System and method for performing an ocular irradiation procedure

ABSTRACT

A method and system for performing an ocular irradiation procedure on a patient&#39;s eye is disclosed. The system includes a head support for supporting the patient&#39;s head, an eye-contact device attachable to the front portion of the patient&#39;s eye, to stabilize the position of the eye; and a position detector for determining the position of the contact device in the external coordinate system. A source of a collimated electromagnetic radiation beam in the system is controlled by a beam-positioning assembly for positioning the beam source such that the beam, when activated, is aimed along a selected path at a selected coordinate in the external coordinate system corresponding to a selected target region in the patient&#39;s eye.

FIELD OF THE INVENTION

The present invention pertain s generally to a system and method forperforming an ocular irradiation procedure on a patient's eye.

BACKGROUND

A number of treatment and surgery procedures, typically involvingirradiating one or more selected targets in the eye, require a patient'seye to be stabilized or positioned prior to and/or during treatment. Forexample, refractive laser surgery involves ablating corneal tissue ofthe eye with an ultra-fast, ultra-short pulse duration laser beam, tocorrect refractive errors in a patient's eye. To achieve ablation,refractive laser surgery requires a laser beam to be precisely focusedto a very small focal spot within the cornea. As such, the patient's eyemust be stabilized, and either the laser system must be properly andprecisely aligned with the patient's eye, or the patient's eye must beproperly and precisely aligned with the laser system.

In order to achieve proper alignment of the eye of the patient relativeto the laser system, the system alignment settings and operatingparameters must be well defined, steadfastly maintained, and frequentlyverified. Accurate and precise refractive surgery requires the cornealtissue be photoablated when the eye is substantially stabilized orstationary. Patient comfort and safety are also a consideration whenholding the eye stationary and conducting laser surgery. Likewise,ocular radiotherapy treatment requires the eye to be stabilized anddynamically positioned during treatment.

In order to achieve the goal of maximizing results while minimizingrisks to the patient during such eye treatment, it is important toeliminate, or at least significantly reduce, as many system errors aspossible. This includes the improper alignment of the patient's eyerelative to the treatment system. Alignment errors may result fromeither a misconfiguration of the system, or from the patient'sinteraction with the system. Insofar as patient/system interaction isconcerned, any voluntary or involuntary movement of the patient's eyeduring treatment can significantly alter the alignment of the eyerelative to the treatment system. It is necessary, therefore, to holdthe eye of the patient stationary during these procedures.

In addition to the operational issued discussed above, patient safety isalso a concern. In particular, when the eye is in direct contact withthe system, the magnitude of the interactive forces that are exerted onthe eye are of concern. The variety of events that can cause theseforces to exceed safety limits need to be avoided. Thus, there is a needfor a system which can physically manipulate the position of the eye,prevent undesired eye movement during treatment, provide needed safetyprecautions, and function as a positional reference between the surfaceof the eye, selected internal anatomy of the eye (e.g., the macula oroptic nerve), and the system. The present system is designed to meetthese needs.

SUMMARY OF THE INVENTION

The invention includes, in one embodiment, a system for performing anocular irradiation procedure on a patient's eye. The system includes (a)a head support for supporting the patient's head, (b) an eye-contactdevice attachable to the front portion of the patient's eye, tostabilize the position of the eye relative to the eye-contact device;(c) means for determining the position of the patient's eye, with suchstabilized with respect to the contact device, and with the patient'shead supported in the head support, in an external coordinate system,(d) a source of a collimated irradiation beam, and (e) abeam-positioning assembly for positioning the beam source in theexternal coordinate system such that the beam, when activated, is aimedalong a selected path at a selected coordinate in the externalcoordinate system corresponding to a selected target region in thepatient's eye.

The eye-contact device may include a concave eye-contact surface adaptedto be placed against the front surface of a patient's eye, and areservoir in fluid communication with the contact surface, by which anegative pressure, e.g., a vacuum of between about 20 to 50 Hg, can beapplied between the eye and the contact surface, to stabilize theposition of the eye with respect to the contact device. In thisembodiment, the system may further include a biasing mechanismoperatively connected to the contact device for biasing the contactdevice against the eye with a force sufficient to the hold the contactdevice against the eye, when the eye is stabilized with respect to thedevice by application of a negative pressure between the eye and thedevice's contact surface. An exemplary force is between 1-25, typically5-20, gram-force.

The determining means may include a position detector for determiningthe position of the contact device, and thus the position of thepatient's eye attached to the contact device, in the external coordinatesystem. In this general embodiment, the position detector may include aplurality of beam elements mounted on the contact device, for directingbeams in accordance with the position and orientation of the beamelements, sensors for detecting the directions of the beams, and aprocessor for determining from the detected beam directions, theposition and orientation of the contact device in the externalcoordinate system.

The system may further include an eye-positioning assembly for movingthe eye-contact device to place the device at a selected position in theexternal coordinate system, and the position detector may be operable todetermine the position of the contact device in the external coordinatesystem, with such placed at said selected position. Thee ye-positioningassembly may be operable to adjust the angular position of the contactmember with respect to the patient's head, and the position detector maydetect an angle of a beam emanating from the contact member. Theeye-positioning assembly may include an arm that is pivotally attachedto the eye-contact member, and an arm control mechanism for controllingthe movement of the arm in at least one direction in the externalcoordinate system, and the position detector may be operable todetermine the position of the contact device in the external coordinatesystem from the position of the eye-positioning assembly arm in theexternal coordinate system.

The determining means includes a reference-beam light source operativelyconnected to the irradiation-beam source, for producing a referencelight beam along a path coincident with the collimated irradiation beamproduced by the irradiation beam source, and the beam-positioningassembly may be operable to place the irradiation beam source at aposition such that the collimated light beam is aimed at the selectedtarget region of patient's eye.

For use in treating macular degeneration in a patient eye, the beamsource may be a source of soft collimated x-rays, and the beam-positionassembly may be operable to position the beam source to direct acollimated x-ray beam at the macular region of the eye, along a paththrough an outer side region of the eye that makes an angle with an axisnormal to the cornea of the eye, between about 5 and 45 degrees.

In another embodiment, the invention includes a method for performing anocular irradiation procedure on a patient's eye, by the steps of: (a)supporting the patient's head in a head support, (b) attaching to thefront of the patient's eye, an eye-contact device effective to stabilizethe position of the eye relative to the contact device; (c) with theeye-contact device placed to a selected position, and with the patient'shead supported in the head support, determining the position of aselected target region of the patient's eye in an external coordinatesystem, (d) positioning a source of a collimated irradiating beam in theexternal coordinate system such that the source beam, when activated, isaimed along a selected path at a selected coordinate in the externalcoordinate system corresponding to a selected target region in thepatient's eye, and (e) activating the beam source.

Attaching step (b) may include placing against the front portion of thepatient's eye, a concave contacting surface of an eye-contact device,and applying a negative pressure between the eye and the contactsurface, thus to stabilize the position of the eye with respect to thecontact device, and which further includes biasing the contact deviceagainst the eye with a force sufficient to the hold the contact deviceagainst the eye, wherein the position of the eye is stabilized withrespect to the device. The negative pressure applied to the contactdevice may be between 20 mm Hg and about 50 mm Hg. An exemplary force isbetween 1-25, typically 5-20, gram-force.

The method may further includes, after attaching the eye to theeye-contact device, moving the contact device to place the device at aselected position in the external coordinate system, and step (c) mayinclude determining the position of the ocular device in the externalcoordinate system, with such placed at its selected position. Moving theeye-contact device to place the device at a selected position in theexternal coordinate system may include directing an incident light beamonto a reflective surface of the contact member, detecting the angle ofthe beam reflected from said surface, and adjusting the angular positionof the contact member until the incident light beam is coincident withthe reflected light beam.

Determining the position of a selected target region of the patient'seye in an external coordinate system includes aiming a collimated lightbeam along a path coincident with the collimated electromagnetic beamproduced by the beam source and positioning the light beam until it isaimed at the selected target region of patient's eye.

For use in treating macular degeneration in a patient eye, step (d) mayinclude positioning a collimated x-ray beam source to direct acollimated x-ray beam at the macular region of the eye, along a selectedpath through an outer side region of the eye that makes an angle with anaxis normal to and through the center of the cornea of the eye, ofbetween about 5 and 45 degrees. The treatment method may includerepeating steps (d) and (e) at each of a plurality of different paths ofthe collimated x-ray beam.

These and other objects and features of the invention will be more fullyappreciated when the following detailed description of the invention isread in conjunction with the accompanying figures.

BRIEF DESCRIPTION OF THE FIGURES

The figures and the associated descriptions are provided to illustrateembodiments of the disclosure and not to limit the scope of thedisclosure. Throughout the figures, reference numbers are reused toindicate correspondence between referenced elements. The figures are insimplified form and are not necessarily precise in scale. In referenceto the disclosure herein, for purposes of convenience and clarity only,directional terms, such as top, bottom, left, right, up, down, over,above, below, beneath, rear, and front are used with respect to theaccompanying figures. Such directional terms are not to be construed aslimiting the scope of the invention in any manner.

FIG. 1 illustrates a top view of one embodiment of a system forcontrollably positioning and/or stabilizing the eye of a subject fortherapeutic treatment;

FIGS. 2A-2B illustrate top views of an embodiment of a system forengaging the eye of a subject;

FIGS. 3A-3D illustrate top and perspective views of the contact deviceand pivotable control arm in accordance with preferred embodiments ofthe invention;

FIGS. 4A-4E depict an exploded view (FIG. 4A), and connecting views(FIGS. 4B-4E) of the contact device in accordance with certainembodiments of the invention;

FIGS. 5A-5B depict perspective views of the contact device without thecontrol arm attached (FIG. 5A) and with the control arm attached (FIG.5B) in accordance with preferred embodiments of the invention;

FIGS. 6A-6C depict perspective views of an contact device and controlarm being reversibly engaged with the system in accordance with oneembodiment of the invention;

FIGS. 7A-7C illustrate a method of engaging and positioning an eye of asubject in accordance with one embodiment of the invention;

FIGS. 8A-8B illustrate perspective views of the contact device out ofalignment with the system (FIG. 8A) and in substantial alignment withthe system (FIG. 8B) in accordance with preferred embodiments of theinvention;

FIG. 9 is a frontal plan view of an embodiment of an eye-contact memberwith no aperture included within the eye-contact member;

FIG. 10 is a frontal plan view of an embodiment of an eye-contact memberwith a circular shaped aperture offset from the center of theeye-contact member;

FIG. 11 is a frontal plan view of an embodiment of an eye-contact memberwith an irregular shaped aperture offset from the center of theeye-contact member;

FIG. 12 is a frontal plan view of an embodiment of an eye-contact memberwith an heptagonal shaped aperture offset from the center of theeye-contact member;

FIG. 13 is a frontal plan view of an embodiment of an eye-contact memberwith a plurality of circular shaped apertures offset from the center ofthe eye-contact member;

FIG. 14 is a frontal plan view of an embodiment of an eye-contact memberwith a diamond shaped aperture offset from the center of the eye-contactmember;

FIG. 15 is a frontal plan view of an embodiment of an eye-contact memberwith a circular shaped aperture offset from the center, and located atthe edge, of the eye-contact member;

FIG. 16 is a frontal plan view of an embodiment of an eye-contact memberwith a kidney shaped aperture offset from the center of the eye-contactmember;

FIG. 17 is a frontal plan view of an embodiment of an eye-contact memberwith a circular shaped aperture offset from the center, and located atthe edge, of the eye-contact member;

FIGS. 18A-B are frontal plan views of embodiments of an eye-contactmember with up to one half of the eye-contact member removed (FIG. 18A),and more than one half of the eye-contact member removed (FIG. 18B);

FIG. 19 is a frontal plan view of an embodiment of an eye-contact memberwith a plurality of radially extending slots emanating from the centerof the eye-contact member;

FIG. 20 is a side view of the eye-contact member of FIG. 19 showing aplurality of radially extending slots emanating from the center of theeye-contact member;

FIG. 21 is a frontal plan view of an embodiment of an eye-contact memberwith a plurality of circular shaped apertures increasing in size andradially spaced from the center of the eye-contact member;

FIG. 22 is a side view of the eye-contact member of FIG. 21 showing aplurality of circular shaped apertures increasing in size and radiallyspaced from the center of the eye-contact member;

FIG. 23 is a frontal plan view of an embodiment of an eye-contact memberwith a grid of apertures within the eye-contact member;

FIG. 24 is a side view of the eye-contact member of FIG. 23 showing agrid of apertures within the eye-contact member;

FIG. 25 is a flow chart illustrating one method of utilizing the systemfor stabilizing and positioning an eye for treatment;

FIG. 26 is a flow chart illustrating a method of utilizing the systemfor treating an eye with radiation in accordance with one embodiment ofthe invention; and

FIG. 27 is a flow chart illustrating a method of utilizing the systemfor laser treating an eye in accordance with another embodiment of theinvention.

DETAILED DESCRIPTION

Reference will now be made in detail to disclosed embodiments of theinvention, examples of which are illustrated in the accompanyingfigures.

I. Definitions

Unless otherwise indicated, all technical and scientific terms usedherein have the same meaning as they would to one skilled in the art ofthe present invention. It is to be understood that this invention is notlimited to the particular methodology and protocols described, as thesemay vary.

As used herein, “accommodation” refers to the ability to change focusfrom distant objects to near objects, which ability may tend to diminishwith age.

The term choroid” refers to the highly vascular layer of the eye beneaththe sclera.

As used herein, “ciliary muscle” refers to a muscular ring of tissuelocated beneath the sclera and attached to the lens via zonules.

As used herein, “conjunctiva” refers to the thin, transparent tissuecovering the outside of the sclera. In some embodiments of theinvention, reference is made to one or more devices or systems of theinvention in contact with outer structures of the eye, such as thesclera. In these embodiments, it is to be understood that the device orsystems of the invention may be in contact with the named structure, ormay be in contact with the conjunctiva covering the structure.

As used herein, “cornea” refers to the transparent, avascular tissuethat is continuous with the opaque sclera and semitransparentconjunctiva, and covered by tear film, or corneal epithelium, on itsanterior surface and bathed by aqueous humor on its posterior surface.

As used herein, “limbus” refers to the boundary where the cornea meetsthe sclera.

As used herein, “retina” refers to the light-sensitive layer of tissuethat lines the inner back of the eye and sends visual impulses throughthe optic nerve to the brain.

As used herein “ocular disease” refers to a disease of the eye,including, but not limited to tumors, ocular degeneration, such asmacular degeneration retinopathies, retinitis, retinal vasculopathies,diabetic retinopathies, diseases of the Bruch's membrane and the like.

As used herein, the term “reducing ocular disease” also encompassestreating and alleviating the ocular disease.

As used herein, “sclera” refers to the outer supporting structure, or“white,” of the eye.

As used herein, the “front of the eye” refers at least a central portionof the cornea and may include surrounding structures, such as thesclera.

As used herein, the term “subject” refers to man or any animal that haseyes.

As used herein, “vitreous body” refers to the clear colorlesstransparent jelly that fills the eye posterior to the lens and that isenclosed by a hyaloid membrane.

As used herein, “zonules” refers to a circular assembly of radiallydirected collagenous fibers that are attached at their ends to the lensand at their outer ends to the ciliary muscle.

As used herein, the term “presbyopia,” refers to the inability of theeye to focus sharply on nearby objects. Presbyopia is associated withadvancing age and typically entails a decrease in accommodation.Introduction of treatment, e.g., laser ablation, according to any of theimplementations described herein, preferably increases or facilitates anincrease in accommodation, thereby mitigating effects of presbyopia.

The term “radiodynamic therapy” refers to the combination of collimatedx-rays with a concomitantly administered systemic therapy.

The term “radiodynamic agents” is intended to have its ordinary andplain meaning, which includes, without limitation, agents that respondto radiation, such as x-rays, and agents that sensitize a tissue to theeffects of radiation.

The term “photodynamic therapy” refers to a therapeutic or diagnosticmethod involving use of a photoreactive agent and radiation of asufficient intensity and wavelength to activate the photoreactive agent.The activated photoreactive agent then, through emission of energy,exerts a therapeutic effect or allows for diagnosis through detection ofemitted energy.

The term “photodynamic agents” is intended to have its plain andordinary meaning, which includes, without limitation, agents that reactto light and agents that sensitize a tissue to the effects of light.

The term “radiation therapy” is intended to have its well-acceptedmeaning and can also refer to any treatment performed with an energysource.

As used herein, “treatment” refers to any manner in which one or more ofthe symptoms of a disease or disorder are ameliorated or otherwisebeneficially altered. Treatment also encompasses any therapeutic use ofthe systems herein.

As used herein the term “external coordinate system” refers to acoordinate system that is fixed, such as a room or the fixed element,e.g., base, of a system component. It typically provides a common set ofcoordinates to place in registry, devices which are moving relative toone another, or which cannot be accurately placed at pre-selectedposition in the coordinate system, such as a patient's head.

Diagnostics can also be performed with any type of energy source ortreatment described herein and may be referred to as “radiationdiagnostics.”

The “position” of an object, such as an eye-contact member, in anexternal coordinate system refers to the position of some known point onthe object, as defined by the coordinates of that point in thecoordinate system. The coordinate system may be, for example, athree-dimensional Cartesian coordinate system, in which the object'sposition is defined by x, y, and z coordinates, or a sphericalcoordinate system in which object's position is defined by radius andangle coordinates.

A “biasing force” refers to a force exerted against a patient's head (oreye), typically expressed in terms of units of gram-force, i.e., theforce exerted by the earth's gravity acting on a gram mass.

A “beam-directing element” refers to an element capable of reflecting animpinging beam, such as a light, microwave, or ultrasound beam, onto adetector, or an element that itself is capable of producing a beam, suchas a light beam that is aimed at one or more beam detectors. Thebeam-directed elements are attached to an eye-contact device or assemblyfor purposes of determining the positions of the beam-directingelements, and thus the position of an eye-contact device or assembly towhich they are attached, in an external coordinate system.

A “reservoir” or “vacuum reservoir” refers to an internal chamber orchambers, e.g., array of fluid-carrying tubes, by which a negativepressure applied to an eye-contact device can distributed over thecontact surface of an eye-contact member.

A “pivot joint” refers to a coupling between two mechanical elementsthat allow of the elements to shift, typically in an angular direction,with respect to the other element. Exemplary pivot joints include balland universal joints, both of which provide multiple degrees of freedom,e.g., degrees of angular motion, between the two elements.

II. System for Stabilizing the Eye and for Performing an OcularIrradiation Procedure

A system in accordance with the present invention is shown in FIG. 1 andis generally designated 100. The system 100 functions as an ocularinterface useful for one or more of the following functions: i.controllably stabilizing the eye; ii. physically manipulating eyeposition; iii. limiting eye from movement during treatment; iv.positionally referencing the surface of the eye, its internal anatomy,and/or the system (e.g. to an external coordinate system) v. providingfiducials relative to the eye and relative to treatments performed aswell as monitoring positioning of the fiducials relative to the eye; vi.maintaining corneal lubrication during treatment; vii. provide amechanism to align a treatment device and continuously signal adequatealignment or misalignment. Substantial or total controllablestabilization of the eye is advantageous for a wide variety oftreatment, diagnostic, and/or surgery procedures as described in detailbelow.

The system 100 includes a platform 105 which allows stationaryattachment of one or more of the components of the system, as describedbelow, such that precise positional information regarding the componentsof the system relative to a known coordinate system (e.g, an externalcoordinate system) are capable of being determined. The system defines areference or external coordinate system in which the components of thesystem are registered, such that all of the points can be positioned andaligned with one another at known positions in the external coordinatesystem. The components of the system described may be automaticallypositioned in the coordinate system by a computer interface, as will bedescribed below. Alternatively, some of the components of the system 100may be manually positioned. In another embodiment, one or more of thecomponents of the system 100 are positioned automatically, and one ormore of the components of the system 100 are simultaneously positionedmanually.

System 100 includes an eye-contact device 110 having an eye-contactmember or surface 120 that reversibly engages or couples to the front aneye 130 of a subject 140 (e.g., FIGS. 2A and 2B). Contact device 110 isconnected to a control arm 180 which is part of an eye-positioningassembly 182 for placing the contact device at a selected position inthe external coordinate system, as will be seen below. Preferably,control arm 180 is pivotably connected to contact device 110 asdescribed below. In some embodiments, the control arm releasably detachfrom the contact device or the eye-contact member in case of suddenpatient movement, as will be described below with respect to FIGS.4A-4D. The eye-contact member 120 engagement with the eye 130 maintainsthe eye in substantially stabilized or immobilized position. Alignmentof the eye can be accomplished with the use of the laser device 150,which can provide alignment of the contact device 110 as described infurther detail below. Thus, FIG. 1 illustrates a preferred embodiment ofthe patient ocular interface system 100 of the invention.

With continuing reference to FIG. 1, system 100 is a patient ocularinterface for treatment of an ocular structure with a treatment device160. As noted, the system includes an eye-contact device 110 adapted tomaintain an eye 130 in a substantially stable position. In oneembodiment of the invention, the contact device is configured to providean indication to a sensor that the eye 130 is in substantially the firstposition during delivery of treatment from device 160, located outsidethe eye. In a preferred embodiment, the system includes a communicationlink 185 that communicates information between the contact device 110and the treatment device 160, the information being indicative of aposition of the eye and determining a characteristic of one or moreparameters of the treatment device 160.

Treatment device 160 may include any of a number of devices that providetherapeutic treatment to the eye. Such therapeutic treatments aredescribed in detail below. In general, device 160 is a source or acollimated irradiation beam directed along a selected axis or path 168,such as a source of electromagnetic radiation (e.g., ablating opticalenergy, thermal optical energy, low level therapeutic optical energy, orradiofrequency energy), ultrasound, and magnetic implementations. Thetreatment device 160 includes, in one general embodiment, is an energyemitting source, such as an electromagnetic laser (e.g., a diode laser)and/or radiation source having a predetermined wavelength, an ultrasounddevice with a predetermined pulse, a cautery device with a predeterminedsetting that interacts with desired parts of the eye, a radiofrequencymodule, an ultrasonic component, and combinations thereof. Device 160can further be a surgical implement or manipulator; for example, asurgical probe for intra-ocular brachytherapy or superficialbrachytherapy can be held in position in a similar manner as device 160with the exception that the surgical implement is placed inside the eye.In one preferred embodiment of the invention, the treatment device 160is a source of a collimated irradiation beam, such as a portable sourceof soft-x-ray beams generated by directing soft x-rays from aconventional x-ray source through a collimator. For purposes ofillustration, device 160 will be referred to herebelow as a source 160of a collimated irradiation beam.

Device 160, in some embodiments, can be a diagnostic device. It may bedesirable to hold an eye in a position to obtain fine detaileddiagnostic information about the eye such as OCT, scanning laserophthalmoscopy, CT scan, MRI, or any other device which may send energyinto the eye and be dependent on steadiness of the structure and/or aknown coordinate reference.

A beam-positioning assembly 162 in the system is designed to positionthe beam source 160 in the external coordinate system such that thebeam, when activated, is aimed along a selected path, corresponding tothe beam axis 168, at a selected position in the external coordinatesystem corresponding to a selected target region of the patient's eye.As seen in FIG. 1, the beam-positioning assembly includes a swivel mount164 on which the beam source is mounted for rotation about an axis 163,and a linear guide 166 on which the swivel mount can travel along anaxis 167. Although not shown here, the “height” position of the beamsource can be adjusted along axis 163, so that the beam from the beamsource is at the same height as a target region in the patient eye. Theangular position of the beam source position on swivel mount 164 and thelinear position of the swivel mount on guide 166 can be adjustedmanually, or preferably, is under the control of stepper or servo motorswhich themselves are controlled by a control unit 115, described below.In addition, the mounting on the beam source on swivel mount 164 may bethrough a connection, such as a ball or universal joint, that allows theangle of the beam-source collimated beam, represented by axis 168, to beadjusted “up” or “down” with respect to a the plane representing byplatform 105, for directing the beam at slight upward or downward anglesinto the eye.

A head support or support 170 for stabilizing the head of subject 140 isincluded in system 100, and includes a chin rest 172 (FIGS. 8A and 8B).Head support 170 is, in the embodiment of the invention illustrated inFIG. 1, attached to the platform 105, e.g., by permanent or releasableattachment. In one embodiment, head support 170 includes a motorizedcontrol assembly with position sensors which can be selectivelyactivated to move and reconfigure the head support. Further details ofthe support, and its function is supporting a patient's head, isdescribed below with respect to FIGS. 8A and 8B.

Also included in the system are means for determining the position of aselected target region of the patient's eye in the external coordinatesystem, with the patient's eye stabilized with respect to theeye-contact device, and the contact device moved to a selected position.The coordinate or coordinates thus determined are used by thebeam-positioning assembly to move the beam source in the externalcoordinate system such that the collimated irradiation beam, whenactivated, is aimed along a selected path at the selected eye coordinatecorresponding to the selected target region of the patient's eye in theexternal coordinate system.

In a first general embodiment, the means for determining the position ofa selected eye target includes an eye-positioning assembly illustratedin FIGS. 6A-6C, for positioning the eye-contact device at a selectedorientation or alignment, a detector for determining when theeye-contact device has been moved to the selected orientation, andposition sensors in the eye-positioning assembly for determining thecoordinates of the eye-contact device when moved to the selectedorientation. In particular, FIGS. 8A and 8B depict a mechanism by whichthe contact device 110 can be used to align the eye with laser alignmentsystem 800, including laser device 150. Optionally, the alignmentmechanism also directly aligns a treatment system, such as aradiotherapy system (not shown) in which the radiotherapy system directsits energy toward the eye in relation to the alignment system. Laserpointer beam 810 (which is collinear with the therapeutic beam in someembodiments) is emitted from laser system 800 through a collimatoropening 820 and reflects off the surface of beam-directing mirror 230 ofthe contact device 110. In the non-alignment case depicted in FIG. 8A,the laser pointer beam 810 will not reflect off the surface of mirror230 collinearly with the collimator opening 820, but will be off-axis,as shown by reflection beam 830. The orientation of the laser system 800and/or the contact device 600 can be manually or automatically adjustedby direct visualization of the location of the reflection beam 830 or bysensors that detect the location of the reflection beam 830 and adjustthe laser system 800 to bring the laser reflection beam 830 intoalignment. In the case where the laser pointer is in fact aligned (FIG.8B), the laser pointer beam 810 is reflected, and the laser reflectionbeam 830 is substantially collinear with the laser pointer beam 830.

The eye-positioning assembly used to position the eye-contact device ata selected orientation, as just described, is illustrated in FIGS.6A-6C. The figures show perspective views of the contact device 110attached to a control arm 180 in the positioning assembly, indicated at625, which is being fed into slot 610 of drive mechanism 600. In someembodiments, the contact device 110 of the system can be attached to acoupling component to hold the eye in place. The coupling component canbe attached to the treatment device, but preferably, as shown in FIGS.6A-6C, it is attached at a location separate from the radiotherapydevice, such as a drive mechanism 600 that is attached to a table orplatform 620 which holds the treatment device.

Contact device 110 is preferably disposable such that a separate (e.g.disposable) contact device 110 is employed for each subject and/or use.Alternatively, contact device 110 may be nondisposable and be treated,e.g., with anti-infective agents, prior to being utilized in multiplesubjects' eyes. Drive mechanism 600 is fixed to base 620 throughconnector 640, which is may robotically controlled, but preferablymanually controlled, and has a known coordinate system. In oneembodiment, drive mechanism 600 is fixed in a known, or predetermined,location with respect to the head positioning system (not shown) and/orthe eye of the subject (not shown) and/or the positioning system of theradiotherapy device. Push button 630 allows free manual positioning ofcontact device 110 into and/or out of slot 610. Thus, as illustrated inFIG. 6A, the control arm 180 is not engaged with the drive mechanism600. In FIG. 6B, the control arm 180 is partially engaged with the drivemechanism 600. And in FIG. 6C, the control arm 180 is fully engaged withthe drive mechanism 600 and is fixed in a known, or predeterminedlocation, which allows the eye of the subject to be fixed in a known, orpredetermined location, when contact device 110 engages the eye.

Although not shown, the eye-positioning device includes internalposition sensors operable to detect the position of the end of arm 110in the external coordinate system, in accordance with movement of thearm in a y direction.

In one embodiment of the invention, spatial registration is used incombination with the system to record and monitor the three dimensionalspatial position of the contact device 110 at all times, relative to aknown reference point. One method of accomplishing the registration isthrough the use of a spatially encoded control arm 180, which tracks theposition of the contact device 110. The control arm 180 holds thecontact device 110 at one end, and is mechanically stabilized or fixedto the platform 620 at the other end. The control arm 180 engages drivemechanism 600, allowing at one degree of freedom and up to three or moredegrees of freedom, and may employ encoding devices to accuratelydetermine the position and orientation of the contact device 110relative to the platform. The control arm 180 also allows movement andpositioning of the contact device 110. The control arm 180 is used toaccurately and reproducibly position the contact device 110. Thepositional information of the contact device 110 is then conveyed tolocalization software for registration of the position of the eye. Thevertical or y position of the control arm can likewise be adjustedthrough movement of a drive 615 on which drive mechanism 600 is movablymounted, allowing both the x and y position of the control arm, and theeye-contact device attached to the control arm, to be accuratelydetermined in the external coordinate system. In particular, the systemfunctions to move the control arm to place the eye-contact device at adesired orientation, by the mechanism shown in FIGS. 8A and 8B, and thendetermine the position of the eye-contact device at this orientationfrom the known arm coordinates.

As will be discussed further below, the motion arm includes a biasingmechanism or element, such as a spring or magnetic element, thatoperates to bias the arm and an eye-contact device supported at the endof the arm against the patient. The biasing element, which isrepresented by force arrow 119 in FIGS. 2B, 6A-6C and 8A and 8B, may bea coil spring within or attached to mechanism 60 or a magnetic biasingmechanism, such as an electromagnetic mechanism that swings the arm inthe direction of the patient with a desired biasing force of preferablybetween 1-25 grams, typically 5-20 grams. This mechanism for securingthe contact device to the eye and stabilized the position of the eye isdiscussed below with reference to FIGS. 8A and 8B.

In a second and related general embodiment, the eye-contact device isequipped with a plurality of position indicators that are capable, incombination with detectors located in the external coordinate system, tolocate the position of the contact device in the external coordinatesystem. This type of tool-tracking system, has been described for use inimage guided surgery, where it is necessary to place a movable surgicaltool, and typically also pre-op patient images, in a common surgicalframe of reference containing the patient. In the present application,the position indicators may be three or more beam-directing elementsdesigned to reflect external positioning beams, e.g., microwave beamsfrom known-position beam sources to known-position beam detectors, withthe position of the contact device being determined by a processoroperatively linked to the beam detectors. Alternatively, thebeam-directing elements in the eye-contact device can be equipped with aplurality of LEDs mounted on the device for directing, for example, aplurality of beams at known-position detectors to determine the positioncoordinates of the contact device in the external coordinate system.Such tool registration systems have been described, for example, in U.S.Pat. Nos. 7,139,601, 7,302,288, and 7,314,430, all of which areincorporated herein by reference in their entirety.

In a third general embodiment the position-determining means takes theform of a collimated light-beam assembly, including a laser light sourceand one or more optical components, such as a half-silvered mirror, foraligning the laser beam with the collimated irradiation beam produced bybeam source 160; such that the two beams are essentially coincident,along the same axis 168. In this embodiment, the beam-positioningassembly is moved with respect to the patient's eye until the laser beamis aimed directly onto the selected target region of the patient's eye,e.g., the macula region at the central rear portion of the retina. Ascan be appreciated, this will place the selected target region of theeye in registry with the therapeutic irradiation-beam; that is, thelaser beam acts as a reference beam that functions to place the eye inthe same frame of reference (coordinate system) as the irradiation beam.

More generally, the spatial registration and guidance of the contactdevice 110 may be through optical or electromagnetic sensor detection.In general, cameras or other detectors are mounted either on the system,or optionally in the treatment room, and are used to track and registerthe position of the eye or contact device 110. Cameras or detectors arethen able to determine and record the three dimensional position of thecontact device 110 in real time, and therefore the position of the eyeas it is positioned. A calibration process can be used to determine therelative spatial position of the contact device to a known referenceframe, as well as in combination with optional images. The calibrationinformation can be stored in a reference file on the computer and usedby a software program.

With continued reference to FIG. 1, system 100 also includes a processoror control unit 115 which has a graphical user interface 117 forreceiving instructions from, and presenting information such asalignment and system functionality data to, a system operator. Further,the control unit 115 is in electronic communication with one or more ofthe other components of system 100 described above, e.g., the motorscontrolling the beam-positioning assembly, the motors controlling theeye-positioning assembly, and sensors, detectors and beam sources fordetermining the position of the eye-contact device in the externalcoordinate system, as described above. An electrical cable may be usedto connect control unit 115 to the additional components. Alternatively,the connection between the control unit 115 to one or more of thecomponents of the system is wireless.

Referring now to FIGS. 2A-2B, top-down views of the contact device 110being reversibly and controllably coupled to the cornea 200 and/orlimbus and/or sclera 239 of the eye 130 is schematically illustrated.The eye 130 includes a cornea 200 and a lens 132 posterior to the cornea200. The eye 130 also includes a retina 134, which lines the interior ofthe rear surface of the eye 130. The retina 200 includes a highlysensitive region, known as the macula, where signals are received andtransmitted to the visual centers of the brain via the optic nerve 136.The retina 200 also includes a point with particularly high sensitivityknown as the fovea. The eye 130 also includes a ring of pigmented tissueknown as the iris 138. The iris 138 includes smooth muscle forcontrolling and regulating the size of an opening in the iris 138, whichis known as the pupil. The eye 130 resides in an eye socket 140 in theskull and is able to rotate therein about a center of rotation.

The eye-contact device 110 functions to stabilize the eye in a firstposition to provide interactive support (e.g. stabilization and/orcontrollable movement) for the eye while the eye is being treated. Thecontact device 110 includes a cup or eye-contact member 120 whichcontacts eye 130. The contact member 120 can be positioned on the eye ina variety of positions, and is therefore useful in a wide variety ofocular treatment procedures. In one embodiment, the eye-contact memberis in at least partial contact with the cornea 200. In a preferredembodiment, as illustrated in FIG. 2B, the eye-contact membersubstantially covers but not necessarily touches the cornea of the eye130 when in operative position. In a related embodiment, the eye-contactmember substantially covers the cornea, but only makes contact with thelimbus of the eye on the periphery of the eye-contact member 120, suchthat the cornea is covered, but is not in direct physical contact withthe surface of eye-contact member 120. The contact member 120 ispreferably a curved structure that is substantially centered on the axis235 with the periphery 237 of the contact member 120 in contact with thesclera 239 and overlying the cornea 200. Thus, the curved contact member120 is positioned to create an interior cavity between itself and thecornea.

The curved contact member 120 is preferably shaped with a concaveeye-contact surface that will substantially conform to the anteriorsurface of the cornea 200 of the eye 130. The contact surface of thecontact member 120 preferably has a radius of curvature that is greaterthan about 5 mm. In one embodiment of the invention, the radius ofcurvature of the inner surface of the eye-contact member 120 is 7.38 mm.Likewise, in a preferred embodiment, the radius of curvature of theouter surface of the eye-contact member 120 is preferably 7.38 mm. Itwill be appreciated that a 1:1 ratio of inner and outer curvaturesminimizes or eliminates refraction of energy through the eye-contactmember 120 in certain embodiments of the invention; in this embodiment,the contact member 120 is a simple cup for the eye 130. Alternatively,the inner and outer curvatures may differ to permit desired focusing ordiffraction of energy as it is transmitted through the eye-contactmember 120. In some embodiments, the contact member 120 is produced in avariety of shapes, one or more of which can be chosen for a givenpatient depending on his or her specific anatomy.

As contemplated by the present invention, the eye-contact member 120 canbe made of a number of materials well known in the art. In an exemplaryembodiment of the invention, the contact member 120 is made frompoly(methylmethacrylate), or PMMA. A certain degree of rigidity, orhardness, of eye-contact member 120 is of use in physically couplingwith the eye and with the pivot which attaches to the control arm asdescribed in further detail below. However, the eye-contact member 120includes, in certain embodiments, a certain degree of flexibility, orsoftness, such that the eye-contact member 120 has a degree offlexibility, but still retains an arcuate shape in its resting position.In some embodiments, eye-contact member can break away from the contactdevice at a predetermined position along connector 222, as described ingreater detail below.

Preferably, the eye-contact member can be fashioned from any suitablematerial with attention to biocompatibility. Thermoset and/orthermoplast PMMA are contemplated by the present invention and aresupplied by a number of sources, such as Perspex CQ (ICI Derby,England). Teflon and tantalum are also noted. It is also possible tocoat eye-contact member 120 with biocompatible materials if elements ofthe eye-contact member 120 are not biocompatible. In some embodiments,the eye-contact member 120 contains pigments or dyes. In particularembodiments, the eye-contact member 120 is coated or impregnated withbioactive substances including anti-inflammatory agents/immunomodulatingagents and/or anti-infective agents. Particular eye-contact members willcontain radiopaque, radioactive, fluorescent, NMR contrast or otherreporter materials.

With continued reference to FIGS. 2A and 2B, the contact member forms,with a back plate 121 of the contact device, an internal reservoir 122by which a negative pressure (partial vacuum) applied to the device,through a vacuum port 210, is distributed across the contact surface ofthe device, as can be appreciated. The vacuum port is connected to asuitable vacuum source though a tube 275. In the embodiment illustratedin FIGS. 2A and 2B, the vacuum port 210 is positioned through theeye-contact member 120 such that an air or fluid communication space isformed through eye-contact member 120 to allow air trapped betweeneye-contact member 120 and the anterior surface of the cornea 200 of eye130 to be reversibly removed, thereby reversibly engaging theeye-contact member 120 with the anterior surface of the cornea 200. Inan alternative embodiment not shown, vacuum port 210 is attached toconnector 270 which can contain a hollow lumen along axis 235 througheye-contact member 120 such that air between eye-contact member 120 andthe anterior surface of the cornea 200 is capable of being reversiblyremoved as described above. Vacuum or suction assistance is useful forlocating and adhering the scleral lens base on the eye 130 of thesubject and securing the contact device 110 to the subject's eye 130.Once in a desired treatment position, the contact device 110 can couplewith the system 100 during the treatment procedure, as described below.Following treatment, the contact device 110 can be decoupled from thesystem 110 and removed from the subject.

In one preferred embodiment, negative pressure applied to the eye, forexample, a negative pressure of 20-50 mm Hg, is effective to stabilizethe position of the eye on the device, that is, substantially preventmovement of the eye with respect to the device, but by itself is notsufficient to hold the eye-contact device on the eye. Rather, thecontact device is secured to the eye by a biasing force acting to biasthe device against the patient's eye, acting in combination with thenegative pressure applied to the eye by the device. In the embodimentillustrated, the contact device is secured to the eye by the biasingforce acting through arm 180, where the negative pressure applied to thecontact device functions to prevent the eye form moving with respect tothe device. As noted above, the contact device is typically biasedagainst the eye with a force of between about 1-25, typically 5-25grams, by a biasing spring, electromagnetic force, or the like. Theadvantage of this system is that the negative pressure applied to theeye can be substantially less than that which would be required if thevacuum alone were acting to hold the device to the eye, and thissubstantially lower negative pressure increases comfort and reducesirritation and deformation of the front portion of the eye. The biasingforce is illustrated in the figures, e.g., FIG. 2B, by an arrow 119,which indicates the direction of action of the force in the figures.

When the eye-contact member 120 contacts eye 130, negative pressure isapplied to remove air from between the eye and contact member, tostabilize the position the eye 130 with respect to the contact member. Aprimary vacuum fitting is in fluid communication with the air passage. Avacuum line 275 is connected to the vacuum port 210. Additionally, avacuum pump is in air or fluid communication with the vacuum line 275for evacuating the air trapped between eye-contact member 120 and thecorneal surface 200. Collectively, the vacuum port 210, line 275, andpump (not shown) constitute a primary vacuum subsystem. The degree ofstrength of the vacuum required to seal can be varied, and preferablycontrollably and continuously monitored, by the system of the invention.In one embodiment of the invention, between about 0.5 mm Hg and about 50mm Hg are utilized to provide the negative pressure effective tostabilize the position of the eye with respect to the contact member120. Preferably, the vacuum is between about 20 mm Hg and about 50 mmHg. More preferably, the vacuum force applied is about 25 mm Hg and ismonitored by pressure sensors and/or by directly monitoring the vacuumsource. In some embodiments, the pressure is held passively, forexample, by a bladder. The bladder can be produced such that it canapply a given maximum pressure.

In one embodiment of the invention, one or more pressure sensors areplaced onto the contact surface of eye-contact member 120 such that thepressure of the force being applied by the vacuum, and causing contactbetween eye-contact member 120 and the corneal surface 200 can bemonitored and selectively adjusted. The adjustment of the pressure canbe automated. Throughout the treatment procedure, e.g., radiotherapytreatment, data from the pressure sensors can communicate to the controlunit 115 via a communication link 185. During the treatment andpositioning procedure as illustrated in FIGS. 7A-7C, and discussed indetail below, the interactive forces that are generated between theeye-contact member 120 and the drive mechanism used to moveably rotatethe eye can be monitored by pressure sensors. The force magnitudesexperienced by the pressure sensors, and the differentials between theforce magnitude, can used to determine the magnitude and direction ofthe forces exerted against the eye 130 during the positioning and/ortreatment procedures. In this way, the operation of the system 100 ismonitored to ensure eye safety, and to minimize the risk of unwanteddamage or injury to the eye 130. Specifically, whenever a predeterminedforce threshold is reached, either in the direction or the magnitude ofthe forces exerted on the eye 130, further movement of the subject's eyeis prevented by the control unit 115.

When activated, the primary vacuum subsystem evacuates air throughvacuum port 210. The evacuation of air creates a negative pressure atthe interface of the eye-contact member 120 and the anterior surface ofthe cornea 200 and/or sclera. The present invention also contemplatesuse of one or more sensors to detect whether a vacuum is formed. In theevent the eye-contact member is not properly seated on the eye 130, thepartial vacuum will not form. In this case, an error message isdisplayed for the system operator on the graphical user interface 117 ofthe control unit 115 of FIG. 1. The error message may be an audiomessage, a visual message, or a combination of the two. In oneembodiment of the invention, suction is used to initially engage thecontact device 110 to the eye 130, and following initial engagement, thesuction is removed and the contact device 110 remains on the eyethroughout the treatment procedure. In another embodiment of theinvention, suction is used to initially engage the contact device 110 tothe eye 130, and following initial engagement, the suction force ismaintained throughout the treatment procedure.

By engaging the contact member 120 with the eye 130, the eye 130 becomesfixed in a first position, the patient unable to move the contact memberwith intra-ocular movements. The contact member can, however, be movedusing control arm 180; the movement by the control arm rotates the eyethrough the eye-contact member. Thus, one embodiment of the inventionincludes substantially stabilizing the eye 130 in a selected positionwith the eye-contact member 120.

With continued reference to FIGS. 2A and 2B, contact device 110 alsoincludes a pivot joint or connector 220 which accommodates pivotmovement between the contact member and positioning arm 180, as the armmoves the contact device to a desired orientation in the externalcoordinate system. In a preferred embodiment, pivotable connector 220 isa spherical or ball pivot joint which allows rotation in threedimensions. As seen best in FIGS. 3A and 3B, positioning arm 180 may bereleasably coupled to the contact device through a stem-and-socketarrangement which fastens the end of arm 180 to a socket formed in balljoint 220.

Eye-contact member 110 also includes a beam-directing mirror 230 orother detector or sensor, which in combination with the laser system150, allows the position and rotation of the eye to be placed at adesired orientation or position in the external coordinate system. Asshown, the mirror 230 is parallel to the eye-contact member 120 andprovides a reflective surface to align the contact device 110 to the eyeand to the treatment device. The position of the mirror 230 alsoprovides a known reference to the subject's corneal apex by virtue ofthe contact member fitting closely to the eye upon application of somevacuum. The alignment of the eye-contact member with a reference laserbeam will be described below with reference to FIGS. 8A and 8B.

In one embodiment, the mirror 230 includes a reflective material thatreflects at least one wavelength of light. In some embodiments, thecharacteristic of a treatment device 160, e.g., a radiation beam, isdetermined by the information and includes at least one of a trajectoryof the radiation beam and an emit/not-emit status. In some embodiments,the communication link to the treatment device 160 is an optical link.In some embodiments, the contact device 110 is adapted to align thetreatment device 160 with a visual axis of the eye. Some embodimentsfurther include a camera that visualizes a position of the eye relativeto the contact device 110. In some embodiments, the camera detectsmovement of the eye and communicates data relating to the eye's movementwith imaging software.

In other embodiment, the eye-contact device includes a plurality offiducials and/or a plurality or beam-directing elements by which theposition of the eye-contact member, and thus the position of a patienteye stabilized in the contact member, in an external coordinate systemcan be determined. As noted below, multiple fiducial arrays or multiplebeam-directing arrays may be monitored by camera or beam-sensingdetectors for determining the position of the fiducial or beam-directingelements in the external coordinate system.

In some embodiments, the eye-contact member 110 is attachable to asurface external to the eye. In some embodiments, the eye-contact member110 is mechanically linked to a eye-position assembly that includescontrol arm 180. In some embodiments, the contact device 110 is engagedwith the eye 130 by docking the contact device 110 into position on theeye 130 (e.g., by the physician) so that the center of the holder has acenter in common with the limbus of the eye. This common center is astep in assuring that the treatment device is aligned with the opticalor geometric axis of the eye. With knowledge of the center of the limbusin combination with an eye model, the treatment device 160 can then bedirected about a treatment axis and center of the limbus to delivertreatment, e.g., radiation, to a target region of the eye, e.g., theretina. The position of the eye 130 can also be tracked by a treatmentsystem 160, e.g., a radiotherapy system.

Some embodiments further include a material that is transmissive ofenergy through the contact device 110. In some embodiments, theradiation beam comprises laser light. In some embodiments, the radiationbeam comprises x-rays. Some embodiments further include a material thatis transmissive of energy through at least a portion of the contactdevice 110. Energy sources contemplated by the present invention includeradio waves, microwaves, infrared light, visible light, ultravioletlight, x-rays and gamma rays.

In some embodiments, the energy comprises laser light. In someembodiments, the energy comprises x-rays. In an alternative embodiment,the energy comprises protons for use in proton therapy or gamma rays foruse in gamma ray therapy. In some embodiments, the eye-contact member120 includes a transmissive portion that transmits a first wavelength ofelectromagnetic radiation from outside to inside the eye.

In some embodiments, the first portion is reflective of a secondwavelength of electromagnetic radiation. Thus, the eye-contact member120 may selectively allow transmission of one or more preferredwavelengths of electromagnetic radiation. Eye-contact member 120 mayselectively reflect one or more wavelengths of electromagneticradiation. In one embodiment of the invention, eye-contact member 120selectively allows transmission of one or more preferred firstwavelengths of electromagnetic radiation, and also selectively reflectsone or more second wavelengths of electromagnetic radiation. In oneembodiment, the portion selectively reflecting and/or selectivelytransmitting one or more wavelengths of electromagnetic radiation iscentrally located in the eye-contact member 120. In another embodiment,the portion selectively reflecting and/or selectively transmitting oneor more wavelengths of electromagnetic radiation is off-centered, on theeye-contact member. In one embodiment, the portion selectivelyreflecting and/or selectively transmitting one or more wavelengths ofelectromagnetic radiation is peripherally located in and/or on theeye-contact member 120. In some embodiments, at least one of theplurality of wavelengths of electromagnetic radiation comprises laserlight beams. In some embodiments, at least one of the plurality ofwavelengths of electromagnetic radiation comprises x-ray beams.

FIG. 3A is a side view of contact device 110 illustrating thepivotability of control arm 180 around the spherical pivotable connector220. The control arm/contact device assembly includes a swivelingtiltable head 190 carrying a conical divot or the like providing a goodmating fit. In the embodiment shown, the head 190 of control arm 180 istilted with respect to a spherical coupling 220 positioned within theconical divot of head 190. The coupling includes a hollow interiorwithin control head 190 that is located at the end of control arm 180 orother connector that snap-fits onto and rotatably rides upon a matingconnector 220. In one embodiment of the invention, the swiveling head190 is designed to coincide with the center of mass of the contactdevice. The swiveling and tiltable head 190 permits a wide range ofmotion of the eye-contact member 120 when the spherical pivot isinserted into the hollow interior of head 190 of control arm 180. Thus,movement of the control arm 180 in the X, Y, and/or Z directions asillustrated in FIG. 3A, permits the contact device to be controllablypositioned. Importantly, when the contact member 120 and holder arefixed with vacuum to the eye as shown in FIG. 2, a greater degree offriction is created between the spherical pivot 220 and the head 190 ofcontrol arm 180 so that the eye moves very little after vacuum isapplied. Moreover, the eye pivots around a point toward its posterior asit is pulled by intraocular muscles which rotate the eye around thisposterior point. When the eye-contact member is coupled to the eye, theeye and the holder are locked together at the pivot point of each. Theintra-ocular muscles cannot move the contact member around its pivotwhich is the only way the contact member can move. Arm 180 can movecontact member 120 through spherical bearing 220. Similarly thepatient's face or head can move the contact member by translation oftheir head or body which would similarly induce a movement aboutspherical pivot 220. However, the muscles of the eye cannot move contactmember 120 when it and the eye are held together. As a result of suchrotational articulation and subsequent coupling, including the frictionbetween the hollow interior of head 190 and spherical pivotableconnector 220, the contact device 120 can be positioned on an eye andstabilized. Such rotational positioning of the contact device andcoupling of the pivot points also allows the mirror 230 of the contactdevice to be aimed or aligned with the system within a known coordinatesystem.

The friction between head member 190 and pivotable connector 220 can beincreased or decreased as desired by varying the surface of thepivotable connector 220 and/or head member 190. For example, to decreasethe friction between the pivotable connector 220 and the head member190, a metal may be used which can be electropolished by a predeterminedamount to provide the desired extent of smoothness. Alternatively, oneor both of the surfaces of pivotable connector 220 and head member 190may be dimpled on either a micro or macro level using known surfacefinishing or machining techniques to increase or decrease frictionaccordingly. Additionally, a liquid lubricant, such as glycerin can beapplied to the surface of the pivotable connector 220 to reduce thefriction at the head member 190/pivotable connector 220 interface, asdesired.

Distal end of the control arm 180 has little or no free movement as itsx-y position is controlled manually or automatically. However, once theholder and the eye are coupled to one another, the eye can be positionedby positioning the arm 180 in the X-Y directions or positioning thepatient's head. Arm 180 can have some flexibility in the Z direction,acting as a cantilever, so that the holder 120 on the eye is notcompletely rigid. Alternatively, a mechanism is provided whichcontrollable adjusts the contact member in the z direction.

FIG. 3B is a perspective view of contact device 310 showing a straightcontrol arm 380 for mechanically linking contact device 310 to a systemfor controllably positioning an eye for treatment. In one embodiment,the eye-contact surface of eye-contact member 120 contacts the sclera ofeye 130. In another embodiment, the eye-contact surface contacts thecornea of eye 130. In yet another embodiment, the eye-contact surface ofeye-contact member 120 is in contact with both the cornea and thesclera. In some embodiments, the contact device 110 includes a portionwhich is at least partially opaque or reflective to x-ray energy. Insome embodiments, the eye-contact holder 110 includes at least a portionthat is at least partially transparent to x-ray energy. In someembodiments, the contact device 110 is configured to apply a suction tothe eye 130 through vacuum port 210. Some embodiments further include acontact device 110 that is configured to contact the eye 130 andmaintain a position of the eye. In the embodiment of the inventionillustrated in FIG. 3B, the control arm 180 is generally cylindrical. Asused herein, the term “generally cylindrical” is not limited to aperfectly cylindrical surface, but instead is understood to include anyfaceted or other column or like structure (e.g., an octagonal cylinder,a hexagonal cylinder, etc.). The material strength of the arm iscontrollable such that a thin arm has greater spring than a thick arm.The thicker arm can therefore apply greater force to the eye when thesubject is positioned in the holder 120. In some embodiments of theinvention a strain gauge is used to measure the resistance and/or changein resistance as the control arm 180 is deflected during positioningand/or stabilization of the contact device 110.

FIGS. 3C and 3D illustrate alternative embodiments of contact devices312 pivotably connected to control arms 180 and 380, respectively. Ascan be seen in FIG. 3C, eye-contact member 320 is connected to sphericalpivot 220 through connector 302 off-center of contact member 320. In theembodiment shown, the head 190 of control arm 180 is tilted with respectto a spherical coupling 220 positioned within the conical divot of head190. The coupling includes a hollow interior within control head 190that is located at the end of control arm 180 or other connector thatsnap-fits onto and rotatably rides upon a mating connector 220. Vacuumport 304 is in air or fluid communication with connector 302 which is inair or fluid communication with a space formed through eye-contactmember 320 which is in air or fluid communication at the eye/contactdevice interface when the contact device 312 is positioned on the eye ofa subject.

FIG. 4 illustrates an exploded view of the contact device 110 with eachcomponent of one embodiment of the contact device 110 separated.Eye-contact member 120 can be reversibly coupled to pivotable connector220 at coupling points 224, 226 which can be reversibly coupled tomirror 230 at coupling points 228, 229. Such coupling may includeinterlocking snaps, glue, welding, magnets, etc. The mirror can bepainted, sprayed or applied with a vacuum deposition process. Thecoupling preferably includes one or more magnets, as illustrated inFIGS. 4B-4C.

More generally, FIGS. 4B and 4C and 4D and 4E illustrate two embodimentsof an eye contact device in accordance with one aspect of the inventionin which an eye-contact member is releasably coupled to a positioningarm through releasable coupling members carried on each component of theassembly. In FIGS. 4B and 4C, the assembly is indicated at 422 andincludes an eye-contact member 120 having a first magnet 410 thereon,and an arm-attachment member 190 carrying a second magnet 415 thereon.As seen in FIG. 4C, as the first coupling member 415 is brought towardthe second coupling member 410, the two coupling members couple theeye-contact member 120 with the spherical pivot 220 which mates with thehead 190 of control arm 180 such that the eye-contact member 120 isconnected to the system. This allows the eye-contact member 120 to movetogether with control arm 180 and therefore be in a known positionwithin the coordinates of the system. Thus, in operation, theeye-contact member 120 may be positioned on the eye of a subject priorto magnetically coupling the two coupling members 410, 415. In analternative embodiment, the eye-contact member 120 is positioned on theeye of a subject following magnetically coupling the two couplingmembers 410, 415. The magnetic coupling can also be used as a safetyfeature in that the magnets become uncoupled when force is applied in adirection which is not co-linear with the perpendicular axis to themagnets.

In a similar manner, FIGS. 4D-4E illustrate a snap fit coupling ormechanical coupling between the eye-contact member 120 and control arm180 in a second embodiment of an eye-contact assembly 416. In FIG. 4D asnap or plurality of snaps is disposed on the first snap coupling member417 for snap coupling with a snap or plurality of snaps on the secondsnap coupling receiving member 412.

In the embodiment illustrated in FIGS. 4D-4E, eye-contact member 120 isattached to second snap coupling receiving member 412, which includes abuilt-in divot 420. In this embodiment, the divot 420 includes a femalereceptacle, such as the illustrated conical depression. However, as usedherein, a divot also refers to any other male or female receptacle, orthe like. The divot 420 is capable of receiving a correspondingly sizedand shaped mating tip 430 which is coupled to the first snap couplingmember 417, which is thereby coupled through spherical pivot 220 tocontrol arm 180. Such a control arm 180 is useful for registering theactual physical location of the subject's eye prior to, during, orfollowing a selected treatment procedure. The registration can beaccomplished using known coordinates within the system, or by obtainingimages. Such images are typically stored in memory of an image-guidedtreatment computer workstation.

As seen in FIG. 4E, as the first snap coupling member 417 is broughttoward the second snap coupling receiving member 412, the two couplingmembers couple the eye-contact member 120 with the spherical pivot 220which mates with the head 190 of control arm 180 such that theeye-contact member is connected to the system. This allows theeye-contact member 120 to move together with control arm 180 andtherefore be in a known position within the coordinates of the system.Thus, in operation, the eye-contact member 120 may be positioned on theeye of a subject prior to snap coupling the two coupling members 410,415. In an alternative embodiment, the eye-contact member 120 ispositioned on the eye of a subject following magnetically coupling thetwo coupling members 410, 415. That is, the releasable coupling membersin the assembly are deformable, typically plastic, members withcomplementary interlocking shapes.

The snap fit or magnetic fit is not only of structural importance butcan provide for an emergency breakaway mechanism if the subject's eyeneeds to move out of the restraint system shown in FIG. 1, as describedin detail below. In a preferred embodiment, the releasable couplingmembers couple the eye-contact member to the arm with a release forcesufficient to allow the device and a patient eye stabilized therein tobe moved by the arm, and to release from one another when anabove-threshold force is applied to the eye, e.g., by sudden eyemovement, or abrupt arm movement, so that the eye is protected frominjury that could result from sudden relative movement between the eyeand contact member. The release force, that is, the force required torelease the two components, may be in the same range, but typicallysomewhat greater than the biasing force used in biasing the contactdevice against the patient's eye, e.g., in the range 10-100 grams.

In one embodiment of the invention, one or more pressure sensors arepositioned on coupling member 410, as illustrated in FIG. 4F. When thecontrol arm 180 is mechanically engaged with the eye-contact member 120,the second magnetic coupling member 415 will contact one or morepressure sensors of which pressure sensors 450, 452, 454 are exemplary.Preferably, when in contact with second magnetic coupling member 415,the pressure sensors 450, 452, 454 lie in a plane that is substantiallyparallel to the plane of the first magnetic coupling member 410. Asillustrated in FIG. 4F, the pressure sensors 450, 452, 454 are eachpositioned an equal distance from the center point of the first magneticcoupling member 410. Also shown in FIG. 4F is the position of thepressure sensors 450, 452, 454 relative to each other. Specifically, thethree pressure sensors 450, 452, 454 are equidistant from each other,i.e., positioned 120 degrees apart. In an alternative embodiment of theinvention, a plurality of pressure sensors are positioned on the secondmagnet coupling member 415.

In operation of this embodiment of the present invention includingpressure sensors, once the eye-contact member 120 is positioned on theeye, and the control arm 120 is coupled to known coordinates within thesystem, the control arm 180 is moved through a “docking” procedurewhereby the control arm 180 is moved to engage with the eye-contactmember 120. During this docking procedure, the two magnetic couplingmembers 410, 415 are engaged. As intended by the present invention, thetwo magnetic coupling members 410, 415 are dimensioned to preciselymatch and reversibly couple to each other with the pressure sensorspositioned therebetween. During the docking procedure, the interactiveforces that are generated between the control arm 180 and theeye-contact member 120 are monitored by the pressure sensors 450, 452,454. It can be appreciated by those skilled in the art that the forcemagnitudes experienced by the pressure sensors 450, 452, 454, and thedifferentials between the force magnitudes, can be used to determine themagnitude and direction of the forces exerted against the eye during thedocking procedure. In this way, the operation of the system is monitoredto ensure patient safety, and to minimize the risk of unwanted damage tothe eye. Specifically, whenever a predetermined force threshold isreached, either in the direction or the magnitude of the forces exertedon the eye, further movement of the control arm 180 toward theeye-contact member 120 is prevented by the control unit. In oneembodiment, when the threshold force is reached, the control arm 180 canonly be moved in a direction away from the eye-contact member 120.

In yet another embodiment, when a predetermined force threshold isreached during the docking procedure or during treatment, such as whenthe subject moves out of position, the eye-contact member 120 can breakaway from control arm 180 such that patient safety is ensured. In thisembodiment of the invention, if the interactive forces that aregenerated between the control arm 180 and the eye-contact member 120reach a predetermined level, the magnetics or snaps may be controllablydecoupled to permit the contact device 120 to break away or disengagefrom control arm 180. Simultaneously, when a predetermined level ofinteractive force or magnitude is reached, and the contact device 120 isdisengaged from the control arm 180, the treatment or diagnosticprocedure may be terminated.

In a similar manner, in accordance with another embodiment of theinvention, when the control arm 180 is used to positionably rotate theeye in a controlled manner, pressure sensors 450, 452, 454 monitor theinteractive forces that are generated between the control arm 180 andthe eye-contact member 120. The force magnitudes experienced by thepressure sensors 450, 452, 454, and the differentials between the forcemagnitudes, can be used to determine the magnitude and direction of theforces exerted against the eye during the positioning procedure. In thisway, the operation of the system is dynamically monitored to ensurepatient safety and to minimize the risk of unwanted damage to the eyethroughout the eye positioning and stabilization procedure.Specifically, whenever a predetermined force threshold is reached,either in the direction or the magnitude of the forces exerted on theeye, further movement of the control arm 180 is prevented by the controlunit. In a related embodiment, whenever a predetermined force thresholdis reached, further movement of the control arm 180 is prevented by thecontrol unit, and the coupling, e.g., snap or magnetic coupling, betweenthe control arm 180 and the contact device 120 is disengaged, decoupledor permitted to break away to ensure patient safety.

In one embodiment of the invention, when the predetermined forcethreshold described above is reached, the magnetic field between the twomagnetic coupling members 410, 415 is turned off to allow theeye-contact member 120 to decouple from the control arm 180. In anotherembodiment, the treatment system is turned off when the predeterminedforce threshold described above is reached. In yet another embodiment,when the predetermined force threshold described above is reached, themagnetic field between the two magnetic coupling members 410, 415 isturned off to allow the eye-contact member to decouple from the controlarm 180, and the treatment system 160 is turned off or prevented frombeing turned on such that the safety of the eye is continuouslymonitored and dynamically maintained throughout the eye positioningand/or treatment procedures.

In one embodiment the entire contact device 110 is molded as a singlecomponent. The contact device 110 includes, in one embodiment, anoptical or other communication between the system 100 and the eye 130 byinhibiting movement of the subject. The contact device contains, in someembodiments, one or more of a radiotransmitter, a laser pointer, and/orfeatures which can be captured on a camera so that the eye can belocated in three-dimensional space.

Referring again to FIG. 4A, the contact device 110 contains, in someembodiments, a mirror 230. The mirror 230 can function as a beamreflector to indicate alignment or misalignment of the laser device 150and/or the treatment device 160, e.g., a radiotherapy device. As thecontact device 110 is positioned in contact with the eye, a properengagement and alignment between the contact device 110 and the systemis achieved. To this end, the laser light source 150 that is mounted onthe platform is used to verify and monitor proper alignment. The lightemanating from the light source is used to create a pattern of reflectedlight that is observable by the system operator, or in some embodiments,by an automated system. Referring now to FIGS. 8A-8B, an exemplary pathof reflected light 830 is shown relative to the path of the source light810. Importantly, when the pattern of reflected light 830 is reflecteddirectly back along the path of the source light 810, the contact device110 is properly engaged and aligned with the system. If, however, thecontact device 110 is not properly or fully aligned with the laser 800,the path of reflected light 830 will be displaced or distorted from itspreferred orientation. In this situation, as shown in FIG. 8A, the pathof reflected light 830 relative to the path of the source light 810emanating from the distal end 820 of laser 800 is indicative of animproper alignment. Further, the system operator can observe themisaligned path of reflected light directly, or on the graphical userinterface, and properly align the contact device 110.

For example, the mirror 230 will reflect a light such as a laser pointeror an LED. The light originates on the laser device 800 and/or treatmentdevice, and its reflection from the mirror 230 is indicative of thedirection of the mirror relative to the laser device 800 and/ortreatment device. The mirror 230 can be parallel to the surface of thecornea, and therefore, a beam perpendicular to the mirror isapproximately perpendicular to the cornea. If a lumen, such as the lumen250 as shown in FIGS. 4B-4F through the center of the mirror is present,and the eye-contact member 120 is transmissive of light at its center, aperpendicular beam to the cornea will travel through the optical orgeometric axis of the eye and reach the center of the posterior pole ofthe eye. The lumen notwithstanding, the beam being reflected from themirror 230, also represents the optical axis of the eye.

In some embodiments, the mirror 230 is a so-called “hot mirror” or a“cold mirror” in which the mirror 230 reflects some wavelengths andtransmits others. For example, a “hot mirror” can reflect an infraredlaser pointer and transmit visible light so that the patient or treatingphysician or a camera will be able to see through the lens. A “coldmirror” will transmit infrared and reflect visible so that a visiblelaser pointer can be reflected while infrared can be transmitted; coldmirrors can be used, for example, in cases where it is desired toutilize an infrared fundus camera during treatment.

As noted above, in some embodiments, contact device 110 can includematerial that is radiotranslucent, or that permits at least someradiation to pass. In some embodiments, the radiotranslucent material ofthe coupling device can be configured to permit the passage of thetherapeutic x-ray beams during treatment. For example, the contactdevice can engage the eye to maintain position of the eye, and the x-raybeams can be directed to target eye tissue with a trajectory that passesthrough at least a portion of the contact device 110. Accordingly, atreatment planning system can plan x-ray beam trajectories withoutsignificant consideration of where the contact device engages or ispositioned on the eye.

In some embodiments, the contact device 110 can include material that isradiopaque, or that reduces or limits the transmission of radiation. Insome embodiments, the radiopaque material of the contact device 110 canbe configured to limit transmission through the material of radiation,such as, for example, x-ray beams. For example, the contact device 110can engage the eye to maintain position of the eye, and x-ray beams thatare directed to target tissue of the eye will not be permitted to passthrough, or transmission of the x-ray beams through the material will besubstantially limited, the contact device 110. In these embodiments, thecontact device 110 can be used as a shield for critical structures ofthe eye (e.g., the lens, the optic nerve, the cornea, and so forth) bylimiting radiation exposure to these structures.

FIGS. 5A-5B are perspective and enlarged views of contact device 110showing a preferred embodiment of the contact device 110 including thecontact member 120, spherical pivot 220, mirror 230 and vacuum port 210.In this embodiment of the invention, the contact device 110 includes oneor more fiducial markers 240, 242, 244, 246, 248 which define thegeometry of the contact device 110 or geometric relationships betweenthe contact device 110 and additional components of the system and/oreye as described throughout the specification. The fiducial markers, inone embodiment of the invention, contribute to the positional knowledgeof the eye when the contact device 110 is engaged with the eye 130, anda coordinate system is known. Spatial registration can be used recordand monitor the three dimensional spatial position of the contact device110 relative to a known reference point.

In the embodiment illustrated in FIGS. 5A-5B, one or more of thefiducial markers 240, 242, 244, 246, 248 includes an imageable fiduciallocator. The fiducial locator is locatable using one or more imagingsystem modalities. In this embodiment, the fiducial is capable of beingmounted in or on the eye-contact member 120, such as being either flushto, or recessed from, an outer surface of eye-contact member 120.However, in alternative embodiments, the fiducial need not be configuredfor mounting flush to or recessed from contact member 120, and can bemounted to extend from eye-contact member 120. In another embodiment,one or more fiducials are positioned on, within, or on the perimeter ofmirror 230. This allows the mirror 230, along with contact device 110,to be centered or aligned with respect to the limbus or other ocularstructure.

The fiducial may include a liquid or gel housed in a sealed interiorcavity. Preferably, the fiducial is a solid. The solid, gel, or fluidmay be visible by one or more imaging modalities (e.g., MR, CT, etc.).In one embodiment, the fiducial is integrated into the eye-contactmember itself. The imaging fiducial is visible and provides goodcontrast on images produced by at least one imaging modality. In oneembodiment, the imaging fiducial is multimodal (i.e., locatable by morethan one imaging modality), such as by using a mixture of differentimaging fluids, gels or solids that are locatable on different imagingmodalities.

In one embodiment, the one or more of the fiducial markers 240, 242, 244includes a substance that is viewable on a first imaging modality, whileone or more of the fiducial markers 246, 248 includes a substance thatis viewable on a different second imaging modality. In one suchillustrative embodiment, the one or more of the fiducial markers 240,242, 244 includes, or is doped with, a substance having a high atomicnumber (Z), such as barium, titanium, iodine, gold, silver, platinum,stainless steel, titanium dioxide, etc. that provides good contrast on aCT or other radiographic imaging system. In this embodiment, one or moreof the fiducial markers 246, 248 include gadopentatate dimeglumine,gadoteridol, ferric chloride, copper sulfate, or any other suitable MRIcontrast agent, such as described in chapter 14 of Magnetic ResonanceImaging, 2nd ed., edited by Stark and Bradley, 1992, which isincorporated herein by reference.

In an alternative multimodal embodiment, the fiducial marker isconstructed of a substantially solid plastic or other material that ishygroscopic, i.e., capable of receiving and retaining a fluid, such asan imaging fluid that is viewable on an imaging system (e.g., an MRIimaging system or the like). In a further embodiment, the plasticforming the fiducial marker is doped or otherwise includes a substancethat is viewable on a different imaging system, such as, for example, aCT or other radiographic imaging system. Illustrative examples of solidplastics that can be made hygroscopic include, among other things, nylonand polyurethane. Using a hygroscopic material avoids the complexity andcost associated with manufacturing a sealed cavity for retaining animaging fluid. Moreover, by adapting the solid hygroscopic plastic forimaging using a first modality, and by using the imaging fluid forimaging using a second modality, each of the solid and the fluid can beseparately tailored toward providing better contrast for its particularimaging modality.

In a further embodiment of the fiducial markers illustrated in FIGS.5A-5B, the outer surface of one or more of the fiducial markers isreflective of light or other electromagnetic energy. Consequently, it islocatable by a camera in an optical positioning system that is coupledto an image-guided workstation (e.g., during subject registration). Oneadditional function of such fiducials is measurement calibration wherethe distance between fiducials is used to calibrate distance on orwithin the eye. In one such example, the outer surface of the imagingspherical fiducial marker includes light-reflective microspheres (e.g.,embedded in an adhesive covering the fiducial or eye-contact member120). In another such example, the outer surface of the fiducial iscovered with an adhesive-backed light-reflective tape, such asSCOTCHLITE 9810 Reflective Material Multipurpose Tape sold by MinnesotaMining and Manufacturing Co. (“3M”), of Saint Paul, Minn.

In one embodiment of the invention, the spherical pivot 220, mirror 230and/or the control arm 180 includes one or more fiducial markers. In analternative embodiment of the invention, the one or more fiducialmarkers are configured to be locatable by a remote positioning system aswell as imagable using one or more imaging modalities. In one suchembodiment, the outer surface of the eye-contact member is configured tobe light reflective, such as discussed above. The fiducial markers arestill advantageously locatable using one or more imaging modalities(e.g., MR, CT, or other imaging system providing 3D or other internalimages within a subject) as well as also being locatable external to thesubject, such as by using a remote camera or like component of anoptical or other positioning system, e.g., that is coupled to animage-guided workstation. In one embodiment, this permits automaticregistration of the actual location of the subject's eye (e.g., usingcameras to locate the light reflective fiducial markers) to pretreatmentimages of the system on which additional imageable fiducial markers arepositioned. This eliminates the need to register the eye of the subjectby inserting an optically-locatable positioning control arm onto thecontact device, and eliminates the need for other absolute positionreference, because the fiducial markers themselves are opticallylocatable and registerable to known locations on pretreatment images ofthe system.

FIG. 5B illustrates one embodiment of the control arm 180 coupled tocontact device 110. Control arm 180 is coupled to an image-guidedworkstation or platform (not shown). In this embodiment, control arm 180includes an end that is sized and shaped to permit being coupled tospherical pivot 220. The control arm 180 includes, in this embodiment, aplurality of fiducial markers 520, 522, 524, 526, 528, 530 that arelocatable by a camera or other like device of the optical positioningsystem. The fiducial markers 520, 522, 524, 526, 528, 530 on the controlarm 180 are positioned in a known spatial relationship to each other andto the tip of the control arm 180. By recognizing the locations of thefiducial markers, the optical positioning system is capable of computingthe location of the control arm tip, which is in a known spatialrelationship with the configuration of the fiducial markers. Thispermits the control arm 180 to be used in conjunction with the opticalpositioning system to register the eye of the subject and to furtherplan and/or perform the treatment procedure using an image-guidedworkstation. An image guided treatment computer workstation, which iscapable of displaying previously acquired and loaded pretreatment imagesof a the system. The optical positioning system connected to theworkstation includes an infrared light (or other energy source) thatprovides light that is reflected from the reflective fiducial markers.This permits the reflective fiducial markers on the control arm 180 tobe located and recognized by the cameras.

As seen in FIGS. 5A-5B, an additional component of the contact device110, in some embodiments and as discussed with reference to FIGS. 4B-4Dabove, is a lumen 250 which traverses the contact device 110 and, insome embodiments, extends to the surface of the eye. The lumen 250 canbe used to pass one or more probes such as may be used to determine theaxial length of the eye (e.g., an A-scan). In some embodiments, theprobe includes a laser pointer probe (not shown), which can pointoutward away from the eye of the subject. The outward pointing laserpointer can be used to determine alignment of the device, and thereforethe eye, relative to a treatment device included within the system. Insome embodiments, the laser pointer is used to align the treatmentdevice with an axis of the eye and can be used to turn the treatmentdevice on (when in position) or off (when not in position). In theseembodiments, the subject turns the device on and off, and the treatmentdevice operates when the eye is aligned with the machine and turns offwhen the device is not aligned with the radiotherapy device.

In some embodiments, the contact device 110 can include material that isradiotranslucent, or that permits at least some radiation to pass. Insome embodiments, the radiotranslucent material of the contact device110 can be configured to permit the passage of therapeutic radiationbeams during treatment. For example, the contact device 110 can engagethe eye to maintain position of the eye, and x-ray beams can be directedto target eye tissue with a trajectory that passes through at least aportion of the contact device 110. Accordingly, a treatment planningsystem can plan x-ray beam trajectories without significantconsideration of where the contact device 110 engages or is positionedon the eye.

In some embodiments, the contact device 110 can include both materialthat is radiopaque and material that is radiotranslucent. In someembodiments, the radiopaque material of the contact device 110 can beconfigured to limit transmission through the material of radiation, suchas, for example, x-ray beams, and the radiotranslucent material can beconfigured to permit transmission of radiation (e.g., x-ray beams) topass through the material. The contact device 110 can further beconfigured to provide alignment trajectories along which the x-ray beamswill pass to the target tissue. In some embodiments, the contact device110 can further operate as a tertiary collimator by limiting the beamsize or shape. For example, the radiotranslucent material of the contactdevice 110 can be sized and shaped as the aperture through the secondarycollimator. In such embodiments, when the x-ray beam is emitted throughthe radiotranslucent material, any penumbra at the contact device 110can be blocked by the surrounding radiopaque material. In someembodiments, apertures in the radiopaque material may be providedinstead of radiotranslucent materials. Accordingly, the contact device110 can further provide shielding or targeting functions.

In some embodiments, the contact device 110 can have a radiopaquematerial that comprises substantially a central portion of the contactdevice 110 (e.g., a portion of the eye-contact member 120), and aportion of the contact device 110 extending around a periphery, or theedges, of the central portion comprises radiotranslucent material.Accordingly, the central portion can operate as a shield to structuresof the eye, and the x-ray beams can pass through the radiotranslucentmaterial during radiotherapy. Thus, the contact device 110 can have alarger eye-contact member 120 to engage the eye while still permittingx-ray beams to reach the target tissues substantially unimpeded by theradiopaque material.

FIGS. 6A-6C illustrate perspective views of the contact device 110attached to control arm 180 which is being fed into slot 610 of drivemechanism 600. In some embodiments, the contact device 110 of the systemcan be attached to a coupling component to hold the eye in place. Thecoupling component can be attached to the treatment device, butpreferably, as shown in FIGS. 6A-6C, it is attached at a locationseparate from the radiotherapy device, such as a drive mechanism 600that is attached to a table or platform 620 which holds the treatmentdevice. Contact device 110 is preferably disposable such that a separate(e.g. disposable) contact device 110 is employed for each subject and/oruse. Alternatively, contact device 110 may be nondisposable and betreated, e.g., with anti-infective agents, prior to being utilized inmultiple subjects' eyes. Drive mechanism 600 is fixed to base 620through connector 640, which is may robotically controlled, butpreferably manually controlled, and has a known coordinate system. Inone embodiment, drive mechanism 600 is fixed in a known, orpredetermined, location with respect to the head positioning system (notshown) and/or the eye of the subject (not shown) and/or the positioningsystem of the radiotherapy device. Push button 630 allows free manualpositioning of contact device 110 into and/or out of slot 610. Thus, asillustrated in FIG. 6A, the control arm 180 is not engaged with thedrive mechanism 600. In FIG. 6B, the control arm 180 is partiallyengaged with the drive mechanism 600. And in FIG. 6C, the control arm180 is fully engaged with the drive mechanism 600 and is fixed in aknown, or predetermined location, which allows the eye of the subject tobe fixed in a known, or predetermined location, when contact device 110engages the eye.

In one embodiment of the invention, spatial registration is used incombination with the system to record and monitor the three dimensionalspatial position of the contact device 110 at all times, relative to aknown reference point. One method of accomplishing the registration isthrough the use of a spatially encoded control arm 180, which tracks theposition of the contact device 110. The control arm 180 holds thecontact device 110 at one end, and is mechanically stabilized or fixedto the platform 620 at the other end. The control arm 180 engages drivemechanism 600, allowing at one degree of freedom and up to three or moredegrees of freedom, and may employ encoding devices to accuratelydetermine the position and orientation of the contact device 110relative to the platform. The control arm 180 also allows movement andpositioning of the contact device 110. The control arm 180 is used toaccurately and reproducibly position the contact device 110 Thepositional information of the contact device 110 is then conveyed tolocalization software for registration of the position of the eye.

Another method to accomplish the spatial registration and guidance ofthe contact device 110 is through optical or electromagnetic sensordetection. In this technique, cameras or other concentrated detectorsare mounted either on the system, or optionally in the treatment room,and are used to track and register the position of the eye or contactdevice 110. Cameras or detectors are then able to determine and recordthe three dimensional position of the contact device 110 in real time,and therefore the position of the eye as it is positioned. A calibrationprocess can be used to determine the relative spatial position of thecontact device to a known reference frame, as well as in combinationwith optional images. The calibration information can be stored in areference file on the computer and used by a software program.

FIGS. 7A-7C illustrate a preferred eye stabilizing and positioningembodiment of the invention. In FIG. 7A, contact device 110 is movedtoward eye 130 along directional arrows 710, 712 such that eye-contactmember 120 contacts eye 130. A vacuum is applied through vacuum port 210to remove substantially all air trapped between eye-contact member 120and eye 130, such that contact device 110 is sealingly engaged with eye130. FIG. 7B illustrates the positioned and stabilized eye 130. FIG. 7Cshows downward, or Y-directional movement of control arm 180 of contactdevice 110. In a preferred embodiment, movement of control arm 180 isperformed by a trained medical professional. Upon directionaldisplacement (e.g. X-Y control of arm 180), control arm 180 pivots aboutspherical pivot 220 such that eye 130 is controllably moved and/orpositioned. In one embodiment of the invention, sensor feedback providesthe location of the eye 130. In another embodiment, control arm 180 isconnected to a drive mechanism, as illustrated in FIGS. 6A-6C, whichallows automated control and position information of the eye 130 as itis moved or positioned.

With continuing reference to FIGS. 7A-7C, an exemplary method ofutilizing the system of the invention includes rotating the eye prior toapplication of treatment. The eye can be gripped and rotated an amount,such as, for example about 1 to 2 degrees, or more broadly about 1 to 90degrees, about the center point. In other implementations, the rotationmay range from about 1 to about 45 degrees or more, and/or at differentpoints in time, in different directions and/or in different amounts.Following such rotation, the eye may, or may not, be held in the rotatedposition, for example while some or all of the treatment(s) are applied.After application of some or all of the desired treatment, the eye canbe moved back, to a full or partial extent, to its naturally-occurringorientation and/or can be released such that the eye moves, to a full orpartial extent, back to its naturally-occurring orientation withoutassistance from the system.

In some embodiments of the invention, after application of some or allof the desired eye treatment(s), the eye can be rotated in the oppositedirection to a greater extent than that to which it was first rotated,such as rotation in the counterclockwise direction about 1 to 90degrees. Following any of the rotations of the eye described herein,and/or at any intermediate step, part or all of the eye being rotatedand/or treated may be held (temporarily or permanently) by means inaddition to the contact device 110 illustrated in FIGS. 7A-7C.

In other embodiments of the invention, following an initialstabilization and rotation, or positioning, of the eye, and applicationof one or more treatments to the eye (e.g., radiotherapy), the eye canbe rotated in the same direction to a greater extent than to which itwas first rotated. Then, one or more desired eye treatments can again beadministered. The process can be repeated to form additional eyetreatments to, for example, focus energy on a single spot, e.g., themacula, such that the sclera is minimally impacted. The eye can berotated in the opposite direction (e.g., past the original, naturallyoccurring orientation) to various degrees to facilitate administrationof one or more tissue treatments. Accordingly, the eye can be rotated inboth directions to facilitate administration of treatment such thatpotential scleral damage and/or healing time can be attenuated oreliminated.

In one embodiment of the invention, the system includes a fluiddispenser. Fluids, including water, sterile water or conditioned fluids,such as those described in U.S. Pat. Nos. 5,785,521 and 6,350,123, thecontents of which are incorporated herein by reference, may be added toassist with healing times or otherwise aid the treated tissue. Forexample, fluid may be applied by way of a small air mister, e.g., from alocal or remotely disposed reservoir or dropper, affixed to the system.The fluid may be applied between and/or during application of treatment,to attenuate or eliminate charring and/or wash away blood.Alternatively, fluid may be applied using a sprayer line affixed to thetreatment device, contact device or otherwise affixed on the system. Thesprayer line may include tubing, e.g., clip-on and/or silicone basedtubing, built into the system and a fluid dispensing unit. Thefluid-dispensing input may be activated manually or automatically topower dispensation of fluid.

FIGS. 7A-7C also illustrate the application of a biasing force 155 byarm 180 during an eye-positioning procedure. As noted above, this forceis used to hold the eye-contact member on the eye, such that thenegative pressure between the eye and eye-contact member can function tostabilize the position of the eye, but at a relatively low vacuum. Inthis embodiment of the invention, an eye-contact assembly, indicated at117, includes an eye-contact member 120 and a biasing mechanism forbiasing the eye-contact member against the patient's eye with a force ofbetween 1-25 grams. In the embodiment illustrated, the biasing mechanismis contained within arm 120, and indicated by direction-of-force arrow119. As noted above, the biasing mechanism may take the form of a coiledspring or circuit-activated solenoid that biases the arm in thedirection of arrow 119.

In another embodiment of the system, the eye-contact member may besupported on a track for sliding movement toward and away from the eye,along an axis substantially normal to the axis of the eye, where thetrack may be mounted, for example, on the head support for positioningin up-and-down and left-and-right directions, to place the trackimmediately in front of the patients eye. With this positioning theeye-contact member can then be moved top engage the front of thepatient's eye, with the patient looking straight ahead. Once initialcontact is made, and after removing air from the eye/contact memberinterface, a biasing force can be applied to the contact member to holdto against the eye during a subsequent eye therapy procedure.

FIGS. 8A and 8B depict a mechanism by which the contact device 110 canbe used to align the eye with laser alignment system 800. Optionally,the alignment mechanism also directly aligns a treatment system, such asa radiotherapy system (not shown) in which the radiotherapy systemdirects its energy toward the eye in relation to the alignment system.Laser pointer beam 810 (which is collinear with the therapeutic beam insome embodiments) is emitted from laser system 800 through a collimatoropening 820 and reflects off the surface of mirror 230 of the contactdevice 110. In the non-alignment case depicted in FIG. 8A, the laserpointer beam 810 will not reflect off the surface of mirror 230collinearly with the collimator opening 820, but will be off-axis, asshown by reflection beam 830. The orientation of the laser system 800and/or the contact device 600 can be manually or automatically adjustedby direct visualization of the location of the reflection beam 830 or bysensors that detect the location of the reflection beam 830 and adjustthe laser system 800 to bring the laser reflection beam 830 intoalignment. In the case where the laser pointer is in fact aligned (FIG.8B), the laser pointer beam 810 is reflected, and the laser reflectionbeam 830 is substantially collinear with the laser pointer beam 830. Thesystem includes, in some embodiments, a sensing module that senses aposition of the eye and relays information concerning the position ofthe eye to the position guide. The sensing module can include a portionthat physically contacts the eye, which can include the eye-contactmember 120 positionable on or over the cornea of the eye. The sensingmodule can, in some embodiments, optically sense the position of the eyewith, for example, a laser.

Some embodiments of the invention, as shown in FIGS. 9-24, provide thatthe eye-contact member have one or more apertures or portions ofradiotranslucent material positioned radially around a center of theeye-contact member 120. The apertures can be shaped as circles, squares,rectangles, ovals, curvilinear, irregular, annular, concentric rings,and so forth. In some embodiments, the contact device 110 is configuredto include an aperture or portion of radiotranslucent material only in acenter portion of the device to permit transmission of radiationtherethrough to target tissue.

FIGS. 9-24 illustrate a variety of embodiments of eye-contact membersthat can be used to selectively control the therapeutic energy (e.g.,radiotherapy) emitted through the eye-contact members toward the eye.FIG. 9 shows one embodiment of the eye-contact member 900. As seen, theeye-contact member 900 includes a connector 905 for coupling theeye-contact member 900 to a control arm (not shown) as discussed above.The eye-contact member 900 is positioned onto an exterior surface of theeye. There is no aperture or opening located on the eye-contact member900 as shown in FIG. 9. FIG. 10 illustrates a circular aperture 1010located off center of eye-contact member 1000, which can be coupled to acontrol arm through connector 1005. The circular aperture is preferablytransmissive of energy to the eye of a subject when used in combinationwith a therapeutic treatment device, such as a radiotherapy deviceallowing precise control of energy through the eye onto a predeterminedstructure located within the eye, e.g., the macula. The diameter of theapertures can be of any range suitable for the treatment selected. Inparticular embodiments of the invention, the diameter of the apertureranges from about 25 microns to about 200 microns. A 100 micron apertureis contemplated in one embodiment. In an alternative embodiment, a 200micron diameter aperture is utilized.

FIGS. 11-18 are similar to the eye-contact member 1000, except as setforth below. Accordingly, the eye-contact members described inconnection with FIGS. 11-18 can be used and applied to the eye of asubject in a similar fashion to the eye-contact members 900 or 1000. Forexample, FIG. 11 shows an embodiment of an eye-contact member 1100 thatincludes a connector 1105 and an aperture 1110 formed in the shape of acrescent. FIG. 12 shows another embodiment of an eye-contact member 1200that includes a connector 1205 and an aperture 1210 formed in the shapeof a heptagon. FIG. 13 shows another embodiment of an eye-contact member1300 that includes a connector 1305 and a plurality of apertures 1310,1312, 1314 formed in the shape of circles. FIG. 14 shows anotherembodiment of an eye-contact member 1400 that includes a connector 1405and an aperture 1410 formed in the shape of a diamond. FIG. 15 showsanother embodiment of an eye-contact member 1500 that includes aconnector 1505 and an aperture 1510 formed in the shape of a partialcircle located at the periphery of eye-contact member 1500. FIG. 16shows another embodiment of an eye-contact member 1600 that includes aconnector 1605 and an aperture 1610 formed in the shape of a kidney. Itwill be appreciated that the apertures shown in FIGS. 11-12, 14, 16 and18 are merely exemplary of non-circular apertures. Other shapes andarrangements may also be provided and are within the scope of thepresent invention. FIG. 17 shows another embodiment of an eye-contactmember 1700 that includes a connector 1705 and an aperture 1710 formedin the shape of a partial circle formed at the periphery of eye-contactmember 1700. FIG. 18 shows another embodiment of an eye-contact member1800 that includes a connector 1805 and an overall shape that coversapproximately half the area of an eye relative to the eye-contact member900 of FIG. 9. Thus, the eye-contact member 1800 may allow moretreatment energy and/or easier access to the eye.

The eye-contact members of FIGS. 9-18 preferably have a constantthickness. However, in some embodiments, the thickness of theeye-contact members may vary between the outer periphery and the centerof the eye-contact members. For example, the thickness of theeye-contact member may gradually decrease from the center to theperiphery of the eye-contact member to allow more energy to enter theeye at the periphery than enters nearer the center. The eye-contactmembers are, in some embodiments at least partially and preferablycompletely opaque, outside the one or more aperture regions. The opacityof the eye-contact members may be achieved in any of several differentways. For example, in one embodiment, the material used to form theeye-contact member may be naturally opaque. Alternatively, the materialused to form the eye-contact member may be substantially clear, buttreated with a dye or other pigmentation agent to render a portion orall of the eye-contact member substantially or entirely opaque. In stillanother embodiment, one or both of the surfaces of the eye-contactmembers may be treated physically or chemically (such as by etching) toalter the refractive and transmissive properties of the eye-contactmember making it less transmissive of energy.

In still another alternative, the surface of the eye-contact member maybe treated with a particulate deposited thereon. For example, thesurface of the eye-contact member may be deposited with particulate oftitanium, gold or carbon to provide opacity to the surface of theeye-contact member. Radiopaque materials such as barium or florescentcompounds can also be included. In another alternative, the particulatemay be encapsulated within the interior of the eye-contact member.Finally, the eye-contact member may be patterned to provide areas ofvarying energy transmissivity, as generally shown in FIGS. 19-24, whichare discussed in detail below.

FIG. 19 shows an embodiment of an eye-contact member 1900 that includesa connector 1905 and a plurality of apertures 1910 in the pattern ofradial spokes extending from the connector 1905 to an outer periphery ofthe eye-contact member 1900. The apertures may have the same opacity, oralternatively have opacities that gradually increase or decrease, asdesired. The graduated opacity may be achieved by, for example,providing different degrees of pigmentation to the apertures 1910. Inanother embodiment, energy blocking materials of the type describedabove in variable degrees may be selectively deposited on the surface ofthe eye-contact member 1900. FIG. 20 is a side view of the eye-contactmember of FIG. 19 showing a plurality of radially extending slots 1910emanating from the center 1905 of the eye-contact member.

In a similar manner, FIG. 21 shows an embodiment of an eye-contactmember 2100 that includes a connector 2105 and a plurality of circularapertures 2110, 2112 and 2114 that increase in diameter from the centerto the periphery of eye-contact member 2100. FIG. 22 is a side view ofthe eye-contact member of FIG. 21 showing a plurality of circular shapedapertures 2110, 2112, 2214 increasing in size and radially spaced fromthe center 2205 of the eye-contact member 2200.

FIG. 23 illustrates an embodiment of an eye-contact member 2305 whichutilizes a patterned aperture structure which includes areas rangingthat are opaque 2320 to areas that are transmissive of energy 2310. FIG.24 is a side view of the eye-contact member of FIG. 23 showing a grid ofapertures 2310 within the eye-contact member 2300.

In the embodiments described above, the selected treatment device isindirectly coupled to the contact device through attachments to thesystem. For example, in a preferred embodiment described above, thecontact device is coupled to a control arm which is connected to thesystem through a drive mechanism; and the selected treatment device iscoupled to the system such that the spatial relationship between thecontact device and the selected treatment device can be dynamicallydetermined. In an alternative embodiment of the present invention, thereexists a direct physical connection between the contact device and theselected treatment system. Thus, in some embodiments, the physicalconnection can include a treatment coupling device. The coupling devicehas an eye-contact member which can include, for example, a scleral lensand a treatment device coupling surface. The eye-contact member cancover the cornea and contact the cornea or it can cover the cornea, onlycontacting the sclera. In some embodiments, the eye-contact member cancover and contact both the cornea and the sclera. The eye-contact membercan be a lens in some embodiments, and in alternative embodiments, theeye-contact member can be a substantially transparent window with littleor no refraction. The eye-contact member can be used to retain oculargel or it can be shell with a hole in the center. The eye-contact membercan be customized for an individual patient using imaging modalities,such as for example, an IOL master, optical coherence tomography (OCT),corneal surface mapping, MRI, CT scan, and ultrasound. The eye-contactmember can be flexible or rigid or a composite. One or more flanges canfunction to hold the eyelids apart or can serve as a fiducial for thetreatment device.

Opposite the eye-contact member are treatment device coupling surfaces,or portions. These surfaces, individually or collectively, couple thecoupling device with the radiotherapy system. While the eye-contactmember interfaces with the eye and structures, the treatment portioncouples the eye-contact member to the treatment system. The treatmentportion can link the coupling device to the treatment device in avariety of ways. For example, the treatment portion can couple to thetreatment device via laser pointer, via infrared coupling, via microwavecoupling, via mechanical coupling, via reflection, or via radiofrequencytransmitters.

III. Methods of the Invention

The device of the present invention may be used in a wide variety ofocular treatment methods. Preferred treatment methods include lasertherapy and radiation therapy. As illustrated in FIG. 25, a preferredmethod 2500 of employing the system described above includes preparing asubject's eye for treatment 2510 which can include delivering ananesthetic, taping the upper or lower lid, dilating the eye, measuringbiometric parameters such as axial length, corneal diameter, etc.Following preparation, the subject's head is secured to the system 2520.The contact device is then positioned on the subject's eye as referencedby reference numeral 2530. Positioning of the holder (described above)on the eye is accomplished by aligning the center of the holder, usingthe x,y,z movement, with the center of the limbus. This can be performedas an approximation by a physician while observing the both the holderand the eye of the patient directly or on a computer monitor.Alternatively, an imaging camera can determine the center of the limbusautomatically and aid in the positioning of the holder with its centeraligned with the center of the limbus. In some embodiments, the holderis positioned in place automatically rather than manually by the deviceoperator.

Once the position of the holder relative to the limbus is determined,suction is applied through the holder to appose it to the eye 2532. Withthe holder firmly attached to the eye, the holder (and eye) can be movedinto position relative to the treatment device in known coordinateswithin the system. In the embodiment where the holder contains a mirrorto monitor its reflection, the holder is positioned such that areflection from the mirror is in position. Once the eye is in position,its movement is stabilized 2540 with suction in one example. The eye canthen be positioned to a predetermined location relative to the treatmentdevice, as indicated by numeral 2550. The treatment device is then movedabout, or otherwise positioned relative to, the eye to deliver itstreatment 2560. Alternatively, the treatment device moves into positionabout the eye. Method steps 2550-2560 can be repeated until a desiredtreatment is completed, after which the subject's eye is released fromthe contact device 2570.

As described above and indicated by numeral 2534, a quick release isbuilt into the contact device in some embodiments of the invention. Incase of an emergency or fatigue, the patient can release from the holderby a applying a modicum of force which results in the eye-contact memberbreaking away from the remainder of the contact device. In such a case,the method step returns to the step prior to positioning and securingthe head 2520, or to the step of positioning the contact device on thesubject's eye 2530, as indicated in FIG. 25.

An exemplary method for utilizing the system is now described. Themethod includes preparing the eye for positioning. Such preparationincludes applying eye numbing drops to the eye of the subject. Scleralclearance can be provided by securing the lower eyelid downward withtape or eyelid eversion. The untreated eye is covered with a patch. Thesubject's head is positioned in a head support and the chin is rested ona chinrest. The head may be secured to the head support with straps orthe like. The eye-contact member is placed on the cornea by tilting theeye-contact member to contact the upper portion of the sclera. As theeye-contact member contacts the upper scleral region of the eye, theeye-contact member is tilted downward to achieve full contact with theeye. Suction is then applied, and verified visually and by the vacuumsource which “holds” suction. The contact device is then aligned with alaser, and centered on the limbus. A desired treatment procedure is thenperformed.

In a preferred embodiment of the method of the invention as illustratedin FIG. 26, a method 2600 of treating an ocular structure of an eye witha radiation beam from a radiotherapy system is described, includingcontacting a surface of the eye with an eye-contact member, wherein theeye-contact member comprises a first portion, such that an axis passingthrough the ocular structure also passes through the first portion ofthe eye-contact member; and emitting a plurality of radiation beamstoward the ocular structure 2610, from a radiotherapy system locatedoutside the eye, such that the plurality of radiation beams each have atrajectory that intersects the axis at a treatment site at the ocularstructure, the treatment site being effectively treatable by at leastone of the plurality of radiation beams. In the embodiment illustratedin FIG. 2600, at least a portion of the radiation is transmitted throughthe contact device which has been positioned on the eye. In analternative embodiment, at least a portion of the radiation istransmitted to the eye without contacting any portion of the contactdevice. In yet another embodiment, which can be used as an alternativeor in combination with the embodiments described above, at least aportion of the radiation is reflected off the contact device when thecontact device is positioned on the eye 2630. The radiation treatment iscontinued until a desired effect is achieved 2640.

In another embodiment of a method of the invention 2700, as illustratedin FIG. 27, the cornea is reshaped using the system of the inventiondescribed above. In this embodiment, a laser is emitted toward thecornea of an eye 2710, followed by the desired reshaping of the surfaceof the cornea 2720. According to some embodiments of the invention,applying treatment energy (e.g., radiotherapy or ablating opticalenergy) to tissues (e.g., the conjunctiva or sclera) can refer to tissuetreatment groupings and/or tissue treatment markings corresponding totissue treatment groupings. Treatment can refer to two or more tissuetreatments arranged in a focused spot or spots on the tissue; anonlinear and nonarcuate grouping (e.g., pattern) on the tissue; and/orarranged in a plurality of focused spots, nonlinear and nonarcuategroupings on the tissue. Tissue treatments or groupings of tissuetreatments may include focused spots, random line shapes, (straight,curved, or otherwise), or may include line shapes formed in a patternthat is predetermined based on a treatment customized to a tissue area.

In another embodiment, the system described above is used to stabilizean eye during laser photocoagulation of the retina or during aphotodynamic treatment of the retina. In these treatments, stabilizationof the eye is currently performed by the physician who holds the eyemanually with a lens contacting the eye. A limitation of this techniqueis that the physician can only hold the lens with very limitedpositioning and stabilization ability subject to tremor and shake. Giventhe system above, the physician would be able to apply these treatmentswith confirmation of stability through the system camera stabilizingarm.

Particular implementations of lasers for use on, for example, the scleramay include Er:YAG, Er:YSGG, Er, CTE:YAG, or Cr:YSGG lasers operated atexemplary wavelengths ranging from about 2.7 to 2.9 microns; XeClexcimer lasers operated at an exemplary wavelength of about 308 nm;frequency-shifted solid state lasers operated at exemplary wavelengthsof about 0.15 microns to about 3.2 microns; excimer lasers of ArFoperated at a wavelength of about 93 nm; harmonic generations of Nd:YAGor Nd:YAL or Ti:sapphire lasers operated at wavelengths of about 190 nmto about 220 nm; CO lasers operated at a wavelength of, for example,about 6 microns and carbon dioxide lasers operated at a wavelength of,for example, about 10.6 microns; diode lasers operated at exemplarywavelengths of about 0.8 microns to about 2.1 microns; gas lasersoperated at wavelengths of about 2.6 microns to about 3.2 microns; andother gas or solid state lasers including flash-lamp and diode-laserpumped lasers operated at wavelengths of about 0.5 microns to about 10.6microns; and optical parametric oscillation (OPO) lasers operated atexemplary wavelengths of about 2.6 microns to about 3.2 microns.

Thus, the devices and methods described above are useful, in someembodiments of the invention, to treat conditions of the eye of asubject. Sources of treatment energy, such as electromagnetic energyemitting devices, can be utilized to implement corneal and/ornon-corneal manipulations. According to the architectures and techniquesof some embodiments of the invention, the source or sources (whenutilized in combination) can be activated to direct energy onto and/orinto parts of the eye, such as the conjunctiva and sclera to treatconditions such as presbyopia, wherein the energy affects at least oneproperty of the eye and results in an enhancement in a property of theeye.

In some embodiments of the invention, focusing disorders such as myopiaand hyperopia are treated. Myopia, or nearsightedness, relates to aneyesight refractive abnormality whereby distant objects appear blurredas a result of rays of light entering the eye being brought to focus infront of the retina. Hyperopia, or farsightedness, on the other hand,relates to an eyesight refractive abnormality whereby near objectsappear blurred or fuzzy as a result of light rays being brought to focusbehind the retina.

One variation of hyperopia is presbyopia, which typically is associatedwith a person's lack of capacity to focus at near distances and whichtends to develop and progress with age. Regarding this progression,presbyopia is thought to advance as the eye progressively loses itsability to accommodate or focus sharply for near vision with increasingage of the person. Accordingly, the condition of presbyopia generallysignifies a universal decrease in the amplitude of accommodation of theaffected person.

Myopia and hyperopia can be treated surgically using techniquesincluding corneal interventions, such as reshaping a surface curvatureof the cornea located inside of the limbus area, and non-cornealmanipulations, such as altering properties of the sclera (which islocated outside of the limbus area), ciliary muscle, zonules, or lens.An example of the former treatment includes ablating the surface of thecornea itself to form a multifocal arrangement (e.g., distance vision inone eye and reading vision in another eye according to a treatment planreferred to as monovision) facilitating viewing by a patient of bothnear and far objects. An example of the latter treatment includesintroducing kerfs into portions of the sclera to thereby increaseaccommodation. Non-corneal interventions typically include temporarilyremoving or pulling back the subject's conjunctiva, using forceps andscissors and/or one or more of scalpels, cautery, plasma, and lasermethods, followed by the actual non-corneal manipulations (e.g, formingkerfs in the sclera). After completing the kerfs, the conjunctiva isthen typically sutured back into position.

Electromagnetic energy devices may include, for example, lasers emittinga wide range of wavelengths, such as lasers having wavelengths ranging,for example, from about 0.2 microns to about 3.1 microns. Exemplarylaser beam sizes can range from about 0.005 mm up to about 1.0 mm, or2.0 mm. Exemplary laser energy per pulse values can range from about 0.1mJ to about 50 mJ depending on, for example, the pulse duration and thelaser beam spot size. Typical pulse laser widths may range from about150 nanoseconds to about 1000 microseconds. The areas to be treated canbe pre-traced with a vascular laser or long pulse Er, Cr:YSGG, or longpulse Er:YAG, to minimize bleeding.

In one embodiment of the invention, radiotherapy is administered.Radiotherapy is particularly useful for treating macular degeneration.Macular degeneration is a condition where the light-sensing cells of themacula, a near-center portion of the retina of the human eye,malfunction and slowly cease to work. Macular degeneration is theleading cause of central vision loss in people over the age of fiftyyears. Clinical and histologic evidence indicates that maculardegeneration is in part caused by or results in an inflammatory processthat ultimately causes destruction of the retina. The inflammatoryprocess can result in direct destruction of the retina or destructionvia formation of neovascular membranes which leak fluid and blood intothe retina, quickly leading to scarring. In treating maculardegeneration, the patient's macula is identified as the target region ofinterest. After stabilizing and positioning the eye, in accordance withthe methods described above, a source of soft collimated x-rays beams ismoved to a position to direct the beam at the macular region of the eye,along a path through an outer side region of the eye that makes an anglewith an axis normal to the cornea of the eye between 5-45 degrees, andpreferably at an angle that avoids directing the beam through the lensof the eye. In one preferred treatment method, the beam source is moved,at the same angle with respect to normal, to tilted positions in whichthe beam is aimed at the macula from a slightly elevated position, andfrom a corresponding below-elevation condition, such that the macula isirradiated along different paths, to minimize the radiation seen by theeye along any one path.

Radiotherapy can be used in combination with other therapeutics for theeye. Radiotherapy can be used to limit the side effects of othertreatments or can work synergistically with other therapies. Forexample, radiotherapy can be applied to laser burns on the retina or toimplants or surgery on the anterior region of the eye. Radiotherapy canbe combined with one or more pharmaceutical, medical treatments, and/orphotodynamic treatments or agents. For example, radiotherapy can be usedin conjunction with anti-VEGF treatment, VEGF receptors, steroids,anti-inflammatory compounds, DNA binding molecules, oxygen radicalforming therapies, oxygen carrying molecules, porphyrynmolecules/therapies, gadolinium, particulate based formulations,oncologic chemotherapies, heat therapies, ultrasound therapies, andlaser therapies.

In some embodiments, radiosensitizers and/or radioprotectors can becombined with treatment to decrease or increase the effects ofradiotherapy, as discussed in Thomas, et al., Radiation Modifiers:Treatment Overview and Future Investigations, Hematol. Oncol. Clin. N.Am. 20 (2006) 119-139; Senan, et al., Design of Clinical Trials ofRadiation Combined with Antiangiogenic Therapy, Oncologist 12 (2007)465-477; the entirety of both of these articles are incorporated byreference herein. Some embodiments include radiotherapy with thefollowing radiosensitizers and/or treatments: 5-fluorouracil,fluorinated pyrimidine antimetabolite, anti-S phase cytotoxin,5-fluorouridine triphosphate, 2-deoxyfluorouridine monophosphate(Fd-UMP), and 2-deoxyfluorouridine triphosphate capecitabine, platinumanalogues such as cisplatin and carboplatin, fluoropyrimidine,gemcitabine, antimetabolites, taxanes, docetaxel, topoisomerase Iinhibitors, Irinotecan, cyclo-oxygenase-2 inhibitors, hypoxic cellradiosensitizers, antiangiogenic therapy, bevacizumab, recombinantmonoclonal antibody, ras mediation and epidermal growth factor receptor,tumor necrosis factor vector, adenoviral vector Egr-RNF (Ad5.Egr-TNF),and hyperthermia. In some embodiments, embodiments include radiotherapywith the following radioprotectors and/or treatments: amifostine,sucralfate, cytoprotective thiol, vitamins and antioxidants, vitamin C,tocopherol-monoglucoside, pentoxifylline, alpha-tocopherol,beta-carotene, and pilocarpine.

Antiangiogenic Agents (AAs) aim to inhibit growth of new blood vessels.Bevacizumab is a humanized monoclonal antibody that acts by binding andneutralizing VEGF, which is a ligand with a central role in signalingpathways controlling blood vessel development. Findings suggest thatanti-VEGF therapy has a direct antivascular effect in human tissues. Incontrast, small molecule tyrosine kinase inhibitors (TKIs) preventactivation of VEGFRs, thus inhibiting downstream signaling pathwaysrather than binding to VEGF directly. Vascular damaging agents (VDAs)cause a rapid shutdown of established vasculature, leading to secondarytissue death. The microtubule-destabilizing agents, includingcombretastatins and ZD6126, and drugs related to5,6-dimethylxanthenone-4-acetic acid (DMXAA) are two main groups ofVDAs. Mixed inhibitors, including agents such as EGFR inhibitors orneutralizing agents and cytotoxic anticancer agents can also be used.

Thus, the system of the present invention can be used in someembodiments to provide radiotherapy treatment. A treatment axis whichprovides a reference about which application of the radiation beams areapplied can be coupled to or aligned with a system axis of theradiotherapy system, about which an x-ray source can be rotated. Thex-ray source can rotate about the system axis of the radiotherapydevice, about which the x-ray source can be rotated. The x-ray sourcecan rotate about the system axis with or independent from an imagingsubsystem and its corresponding axis. With the treatment axis alignedwith the system axis, and with the coupling device engaging the eye,trajectories of the radiation beams can be determined to direct theradiation beams to be coincident with the target tissue of the eye ofthe subject. The defined space of the treatment axis, the system axis,the location of the coupling device, and the location of the x-raysource provides a confined coordinate frame that can be used, forexample, for directing orientation and administration of the radiationbeams.

In one embodiment of the invention, radiodynamic therapy isadministered. Radiodynamic agents can be administered eithersystemically or into the vitreous; the region in the eye to be treatedis then directly targeted with radiotherapy as described above. Thetargeted region can be precisely localized using the device of theinvention and/or in combination with an eye model, and then radiationcan be precisely applied to that region. Beam sizes of about 1 mm orless can be used in radiodynamic therapy to treat ocular disorders ifthe target is drusen for example. In other examples, the beam size isless than about 6 mm.

It is further contemplated that the system of the present invention canbe utilized to treat a variety of types of cancer of the eye. Exemplarycancer treatments are described below.

Intraocular melanoma starts from pigment cells called melanocytes, whichare found in the part of the eye known as the the uvea. The uveaincludes the iris, which forms the colored part of the eye; the ciliarybody, which helps change the shape of the lens inside the eye so that itcan focus; and the choroid, which is a very deep layer of the eye.Though it is uncommon, uveal melanoma is the most common primary eyetumor in adults; approximately 1200 people are diagnosed with thedisease each year in the United States. Factors associated with thedisease's development include light skin color, environmental exposureand genetic predisposition.

If the melanoma begins in the iris, it may appear as a dark spot on theeye. However, if it begins in the ciliary body or choroid, symptoms mayappear as vision problems, if at all. In these cases, the disease isusually detected during a routine examination. Chances of recovery andresponse to treatment depend on the location of the melanoma and whetherit has spread. Posterior uveal tract melanomas (those cancers arisingfrom the ciliary body or the choroid—the deeper parts of the eye) aretypically more malignant, with a five-year mortality rate of 30% whenthe tumor has spread to areas outside of the eye. Anterior uveal tractmelanomas (those arising from the iris) have a 2% to 3% mortality rateover five years. Thus, in one embodiment of the invention, intraocularmelanoma is treated using the system of the invention.

Standard treatment for intraocular melanoma typically includes surgicalremoval of the eye, or enucleation. Because of this procedure's effecton a patient's appearance, possible diagnostic uncertainties and thepotential for the cancer to spread, alternative treatments have beenintroduced. These treatments include radiation with radioactive plaques,laser photocoagulation, transpupillary thermotherapy and cryotherapy.Also contemplated is proton beam therapy which has the ability toprecisely target eye tumors without causing any serious damage tohealthy tissue surrounding the eye.

Choroidal metastasis occurs when cancer spreads to the choroidal layerof the eye from another primary site, like the breast. In thesesituations, the goal of treatment is to improve the patient's quality oflife by preserving vision and preventing removal of the eye.Chemotherapy, external beam radiation therapy and proton therapy incombination with the system described above are contemplated by thepresent invention for the treatment of choroidal metastasis such thatthe therapeutic treatment allows for retention of the eye, achieves ahigh probability of local control, and helps avoid vision loss and pain.

Retinoblastoma is an uncommon childhood cancer. It begins in the retina,and accounts for about 3% of cancers in children younger than 15years—about 4 cases per million. It most often occurs before the age oftwo, with 95% of retinoblastoma diagnosed before the age of five. Thetumor may affect one eye (about 75% of cases), or both eyes (25% ofcases). More than 90% of retinoblastoma that does not spread beyond theeye will be cured. Retinoblastoma is sometimes caused by an inheritedgene mutation; when it occurs in both eyes, it is always the result of agene mutation. Treatment of retinoblastoma in accordance with thepresent invention contemplates a multidisciplinary approach, andinvolves treating the cancer as well as retaining vision. If the tumoris especially large, or if there is little expectation of retainingnormal vision, surgery may be considered. Other options includecryotherapy, photocoagulation, chemotherapy and radiation therapy.External beam radiation therapy with protons has been used in selectcases to control tumors. Proton therapy in combination with the systemof the invention is also contemplated by the present invention.

Choroidal hemangiomas are benign vascular tumors that are usually wellcontained, and may cause a decrease in visual abilities. Treatment ofchoroidal hemangiomas is meant to reduce fluid collection under theretina and decrease the size of the tumor. Standard treatment involveslaser photocoagulation, which successfully reattaches the retina, butmay not always completely destroy the tumor. In recent years,radioactive plaque treatment and proton beam radiation treatments havebeen used. Proton beam therapy shares the precise tumor targetingability of radioactive plaques, and is therefore contemplated for usewith the system of the present invention.

In addition to the cancer treatment methods described above, theinvention also contemplates manipulating the eye so as to move criticalstructures away from the treatment axis to deliver therapeutic amountsof radiation to tumors outside, but near, the eye. Thus, in oneembodiment of the invention, the system is used to position the eye forthe treatment of extraocular conditions.

In one embodiment of the invention, the device described above isutilized in combination with other therapeutics for the eye. Forexample, one or more therapy treatments such as cryotherapy,photocoagulation, chemotherapy and radiation therapy can be utilized incombination with the system of the present invention to providetherapeutic treatment of the eye.

From the foregoing, it can be seen how various objects and features ofthe invention are met. While certain aspects and embodiments of thedisclosure have been described, these have been presented by way ofexample only, and are not intended to limit the scope of the disclosure.The methods and systems described herein may be embodied in a variety ofother forms without departing from the spirit thereof. All publicationsand patents cited herein are expressly incorporated herein by referencefor the purpose of describing and disclosing systems and methodologieswhich might be used in connection with the invention.

1. A system for performing an ocular irradiation procedure on apatient's eye, comprising (a) a head support for supporting thepatient's head, (b) an eye-contact device attachable to the frontportion of the patient's eye, to stabilize the position of the eyerelative to the eye-contact device, (c) means for determining theposition of the patient's eye, with such stabilized with respect to thecontact device, and with the patient's head supported in the headsupport, in an external coordinate system, (d) a source of a collimatedirradiation beam, and (e) a beam-positioning assembly for positioningthe beam source in the external coordinate system such that the beam,when activated, is aimed along a selected path at a selected coordinatein the external coordinate system corresponding to a selected targetregion in the patient's eye.
 2. The system of claim 1, wherein theeye-contact device includes a concave contact surface adapted to beplaced against the front surface of a patient's eye, an outer surface,port in fluid communication with the contact surface, by which anegative pressure can be applied between the eye and the contactsurface, to stabilize the position of the eye with respect to thecontact device, and a connector carried on the outer surface of thedevice, and the system further includes a biasing mechanism operativelyconnected to the connector of the contact device for biasing theeye-contact device against the eye with a force sufficient to the holdthe contact device against the eye, when the eye is stabilized withrespect to the device by application of a negative pressure between theeye and the device's contact surface.
 3. The system of claim 1, whereinsaid determining means includes a position detector for determining theposition of the contact device, and thus the position of the patient'seye attached to the contact device, in the external coordinate system.4. The system of claim 3, wherein the position detector includes aplurality of beam elements mounted on the contact device, for directingbeams in accordance with the position and orientation of the beamelements, sensors for detecting the directions of the beams, and aprocessor for determining from the detected beam directions, theposition and orientation of the contact device in the externalcoordinate system.
 5. The system of claim 3, which further includes aneye-positioning assembly for moving the eye-contact device to place thedevice at a selected position in the external coordinate system, and theposition detector is operable to determine the position of the contactdevice in the external coordinate system, with such placed at saidselected position.
 6. The system of claim 5, wherein the eye-positioningassembly is operable to adjust the angular position of the contactmember with respect to the patient's head, and the position detectordetects an angle of a beam emanating from the contact member.
 7. Thesystem of claim 5, wherein the eye-positioning assembly includes an armthat is pivotally attached to the connector of the eye-contact device,and an arm control mechanism for controlling the movement of the arm inat least one direction in the external coordinate system, and theposition detector is operable to determine the position of the contactdevice in the external coordinate system from the position of theeye-positioning assembly arm in the external coordinate system.
 8. Thesystem of claim 1, wherein said determining means includes areference-beam light source operatively connected to theirradiation-beam source, for producing a reference light beam along apath coincident with the collimated irradiation beam produced by theirradiation beam source, and said beam-positioning assembly is operableto place the irradiation beam source at a position such that thecollimated light beam is aimed at the selected target region ofpatient's eye.
 9. The system of claim 1, which further includes a vacuumsource operable to apply a negative pressure of between about 20-50 mmHg to the contact device contact surface.
 10. The system of claim 1, foruse in treating macular degeneration in a patient eye, wherein the beamsource is a source of soft collimated x-rays, and the beam-positionassembly is operable to position the beam source to direct a collimatedx-ray beam at the macular region of the eye, along a path through anouter side region of the eye that makes an angle with an axis normal tothe cornea of the eye, between about 5 and 45 degrees.
 11. A method forperforming an ocular irradiation procedure on a patient's eye,comprising (a) supporting the patient's head in a head support, (b)attaching to the front of the patient's eye, an eye-contact deviceeffective to stabilize the position of the eye relative to the contactdevice, (c) with the eye-contact device placed to a selected position,and with the patient's head supported in the head support, determiningthe position of a selected target region of the patient's eye in anexternal coordinate system, (d) positioning a source of a collimatedirradiating beam in the external coordinate system such that the sourcebeam, when activated, is aimed along a selected path at a selectedcoordinate in the external coordinate system corresponding to a selectedtarget region in the patient's eye, and (e) activating the beam source.12. The method of claim 11, wherein said attaching step (b) includesplacing against the front portion of the patient's eye, a concavecontacting surface of an eye-contact device, and applying a negativepressure between the eye and the contact surface, thus to stabilize theposition of the eye with respect to the contact device, and whichfurther includes biasing the contact device against the eye with a forcesufficient to the hold the contact device against the eye, wherein theposition of the eye is stabilized with respect to the device.
 13. Themethod of claim 12, wherein said biasing includes biasing theeye-contact member against the eye with a force of between 1-25 grams.14. The method of claim 12 wherein said applying includes a negativepressure to the contact device of between 20 mm Hg and about 50 mm Hg.15. The method of claim 11, which further includes, after attaching theeye to the eye-contact device, moving the contact device to place thedevice at a selected position in the external coordinate system, andstep (c) includes determining the position of the ocular device in theexternal coordinate system, with such placed at its said selectedposition.
 16. The method of claim 15, wherein moving the eye-contactdevice to place the device at a selected position in the externalcoordinate system includes directing an incident light beam onto areflective surface of the contact member, detecting the angle of thebeam reflected from said surface, and adjusting the angular position ofthe contact member until the incident light beam is coincident with thereflected light beam.
 17. The method of claim 11, wherein determiningthe position of a selected target region of the patient's eye in anexternal coordinate system includes aiming a collimated light beam alonga path coincident with the collimated electromagnetic beam produced bythe beam source and positioning the light beam until it is aimed at theselected target region of patient's eye.
 18. The method of claim 11, foruse in treating macular degeneration in a patient eye, wherein step (d)includes positioning a collimated x-ray beam source to direct acollimated x-ray beam at the macular region of the eye, along a selectedpath through an outer side region of the eye that makes an angle with anaxis normal to and through the center of the cornea of the eye, ofbetween about 5 and 45 degrees.
 19. The method of claim 18, whichincludes repeating steps (d) and (e) at each of a plurality of differentpaths of the collimated x-ray beam.
 20. The system of claim 2, whereinthe eye contact member is a curved structure which is centered on acenter axis extending through the contact member, substantially normalthereto, and said connector is disposed along the center axis of thecontact member.
 21. The device of claim 2, wherein the eye contactmember is a curved structure which is centered on a center axisextending through the contact member, substantially normal thereto, andsaid connector is disposed along an axis offset from the center axis.22. The device of claim 2, wherein the connector is detachably coupledto the biasing mechanism, allowing the mechanism to break away from theeye-contact member when an above-threshold force is applied by or to theeye.